UMLS:C0027627 - FACTA Search

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Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical effects and side effects were investigated in the adoptive immunotherapy of patients bearing malignant diseases using human leukocyte antigen (HLA)-mismatched allogeneic lymphokine-activated killer (LAK) cells. Allogeneic LAK cells were induced from peripheral blood lymphocytes (PBL) of healthy donors with the same blood types as those of patients. Recently we succeeded in increasing the proliferation rate and enhancing the cytotoxic activity of LAK cells by means of initial stimulation with pokeweed mitogen (PWM, PWM-LAK cells). Five of 12 patients applied in the adoptive immunotherapy showed clinical effects such as partial or complete regression of pulmonary metastases and pleural effusion. All pulmonary metastatic lesions were eliminated in one case by this adoptive immunotherapy combined with chemotherapy. Toxic effects were chillness, fever and general fatigue which were reversible, and no allergic side effects occurred even though allogeneic LAK cells were injected frequently. In the patients who received more than 10(11) of allogeneic LAK cells, anti-HLA class I antibodies appeared without any evidence of autoantibody. However, immunological side effects were never experienced after injection of allogeneic LAK cells even when the anti-HLA class I antibodies existed in the patients; this phenomenon suggests the safety of the adoptive immunotherapy using allogeneic LAK cells. Taken together, allogeneic LAK cells could be considered as alternative therapy for patients with malignancies who could not supply sufficient materials of autologous LAK cells. Recently, LAK cells, particularly PWM-LAK cells were found to obtain significantly potent and prompt lectin-dependent cell-mediated cytotoxicity (LDCC). All tumor cells confluent in microtest plate well could be annihilated by PWM-LAK cells plus PWM less than 8 hours. New immunotherapy using PWM-LAK cells or lectin-stimulated LAK cells with PWM or other lectins is discussed.
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PMID:Use of human leukocyte antigen-mismatched allogeneic lymphokine-activated killer cells and interleukin-2 in the adoptive immunotherapy of patients with malignancies. 146 21

A monoclonal antibody (mAb) directed against the cytokeratin (CK) polypeptide no. 18 specifically expressed in cells derived from simple epithelia was used to detect epithelial tumor cells in bone marrow aspirates. Of 156 patients with colorectal carcinoma, 42 presented with cells at the time of primary surgery. The incidence of positive findings varied considerably with the size and the localization of the primary tumor, the involvement of regional lymph nodes, and the presence of clinically manifest metastases. Applying a sensitive double-staining procedure, we could demonstrate that epithelial cells in bone marrow showed a heterogeneic expression of receptors for epidermal growth factor (EGF-R) and transferrin (Tf-R) as well as of the proliferation-associated Ki67 antigen. Also human leukocyte antigen (HLA) class I antigens differed widely in their expression on the CK-positive cells. Clinical follow-up studies on 85 patients showed a significantly higher relapse rate in patients presenting with CK-positive cells in their bone marrow at the time of primary surgery. Twenty-three patients were monitored for the presence or absence of CK-positive cells in bone marrow over time. The majority of monitored patients (18 of 23) exhibited a constant pattern of immunocytochemical findings during the time of observation. Thus, the technique may be useful in identifying high-risk patients as well as in monitoring adjuvant therapeutic trials.
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PMID:Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization, and prognostic significance. 169 90

The authors have studied in detail human leukocyte antigen (HLA) association in 87 Hungarian patients with thyroid epithelial carcinoma. The authors also examined in a small group of patients, five parameters of cell-mediated immunity and related them to HLA as well as to lymphocytic infiltration of the tumor/normal tissue interface. HLA-DR1 was significantly associated with thyroid carcinoma; the strongest association was in patients with follicular histologic features and DR1 homozygotes were not at greater risk for thyroid cancer. The HLA-DR3 was nonsignificantly increased in patients with papillary or mixed histologic features. The HLA-DR1, 3 heterozygotes were highly associated with follicular carcinoma, carried no risk for papillary carcinoma, and an intermediate risk for tumors with mixed histologic features. Because of the small proportion of DR1, 3 heterozygotes in the follicular and mixed histologic group, its predictive value at the population level was low. Better predictive potential was shown for the phenotype DR1 and/or DR3. Neither metastatic disease nor age at diagnosis (less than 45 years) could be related to HLA phenotypes. Patients in all histologic variants showed some measure of cell-mediated immunity compared to controls. Patients with papillary carcinoma showed an overall better response than those with tumors with follicular or mixed histology. The HLA-DR could not be related to cell-mediated immune response. Patients with papillary carcinoma with a good cell-mediated immune response occurred with much lower infiltration of the tumor boundary with lymphocyte whereas the follicular carcinoma less cell-mediated immunity was associated with dense lymphocytic infiltration, suggesting the biological relevance of lymphocytic infiltration may be different for the two histologic variants.
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PMID:Immunogenetic and immunologic studies of differentiated thyroid cancer. 278 72

Susceptibility to a variety of malignancies has been linked to human leukocyte antigen (HLA) genes, including the HLA class II allele DQB1*0301. To determine whether melanoma risk is associated with HLA class II alleles, molecular oligotyping of HLA class II-DRB1, -DQA1 and -DQB1 genes was performed for 45 patients with melanoma. The DQB1*0301 allele was present in 56% of melanoma patients vs. 27% of 200 local Caucasian controls. This difference was highly significant (Bonferroni's-corrected chi-square p = 0.003, OR = 3.4). No other class II allele tested was present at significantly increased or decreased frequency in melanoma patients. Furthermore, presence of DQB1*0301 in melanoma patients was associated with advanced disease. Melanoma patients carrying the DQB1*0301 allele presented on average with thicker primary tumors (mean 3.7 mm vs. 1.8 mm, 2-tailed p = 0.02) and were more likely to present with regional or distant metastatic disease (stages III-IV, 44% vs. 5%, chi-square p = 0.003), compared to melanoma patients without DQB1*0301. Risk of melanoma incidence or progression may be influenced by DQB1*0301 or a closely linked gene.
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PMID:HLA-DQB1*0301 association with increased cutaneous melanoma risk. 796 Feb 21

Surface expression of human leukocyte antigen (HLA) class I antigens on melanoma lines was evaluated by locus-specific monoclonal antibodies (mAbs) with three different techniques: Fluorescence-activated cell sorting (FACS), immunohistochemistry with cytospin preparation (ICP), and complement-mediated cytotoxicity (CMC). Eleven HLA class I-expressing cell lines developed from metastases were used. Specific expression of HLA loci was examined under routine culture conditions and after 48-h incubation in interferon-gamma (IFN-gamma; 500 U/ml). Loss of allelic expression was seen in one line (586-MEL): Products of genes coding for HLA-A29 and -B44, in strong linkage disequilibrium, were not detectable. HLA-A antigens were consistently detected by all methodologies and minimally affected by pretreatment with IFN-gamma. HLA-B antigens were detectable in 8 of 11 lines by ICP and 3 of 11 lines by CMC. By FACS the supratypic specificity HLA-Bw6 was expressed at low levels in most lines (mean fluorescence 47.2 +/- 13.4 and rose to 259.8 +/- 45.9 after incubation with IFN-gamma; p < 0.001). HLA-Cw antigen detection by CMC correlated with HLA-B (p < 0.01), suggesting that down-regulation and sensitivity to IFN-gamma are shared by the two loci. This low expression of the HLA-B antigens may play a role in the evasion of the host immune response and its up-regulation may be useful in allowing tumor antigen recognition.
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PMID:Locus-specific analysis of human leukocyte antigen class I expression in melanoma cell lines. 808 56

Human primary malignant melanoma is often accompanied by a host response of infiltrating lymphocytes suggestive of tumor antigen-induced immunity and correlated in some tumors with prognosis. Whereas metastatic melanoma deposits typically are not inflamed and contain relatively few lymphocytes and dendritic immune cells, immunization with autologous melanoma-cell vaccine may induce a clinical inflammatory response associated with mononuclear-cell infiltration. In this study, we characterize immune responses to dermal and subcutaneous melanoma metastases in dinitrophenyl (DNP)-pre-sensitized patients immunized with DNP-conjugated melanoma cells. Patients so treated develop cutaneous delayed hypersensitivity responses to DNP-conjugated autologous mononuclear cells, and approximately one-half show clinical evidence of inflammation and regression of metastases within 2-4 months. Whereas pre-vaccination biopsies of metastatic melanoma failed to reveal significant infiltration by lymphocytes, biopsies obtained after vaccination and coincident with clinical inflammation were markedly infiltrated preponderantly by T cells with a CD8+ phenotype. Clustering of these cells about individual degenerating melanoma cells in a manner analogous to "satellitosis" was a consistent feature of this reaction. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen (HLA)-DR by melanoma cells were invariably associated with zones of T-cell infiltration, whereas diminished or absent expression was observed in relatively unaffected regions of tumors. Numerous HLA-DR+, CD4+, CD1-, Leu-1- dendritic cells were also associated with zones of early T-cell infiltration. These data indicate that clinical inflammation and regression of metastatic melanoma induced by autologous melanoma-cell vaccine involves activated T cells with cytotoxic-suppressor phenotype and dendritic cells putatively capable of local antigen presentation. ICAM-1 upregulation on melanoma cells is a likely mediator of ligand interaction between infiltrating T cells and target cells in this model of antigen-induced host anti-tumor response. Structural alterations identified in this setting (e.g., tumor cell satellitosis) may provide additional insight into identifying features of naturally occurring host immune responses to primary cutaneous melanomas.
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PMID:Autologous melanoma vaccine induces inflammatory responses in melanoma metastases: relevance to immunologic regression and immunotherapy. 844 Sep 19

Tumor-infiltrating lymphocytes (TILs) were grown from four distinct anatomic sites from a patient with metastatic melanoma. The metastatic sites included a tumor-involved lymph node, a subcutaneous lesion obtained from the chest wall, a portion of bowel, and adrenal gland. TILs grown from each anatomic site over the course of 20 days in the presence of 6,000 IU/ml recombinant interleukin-2 exhibited comparable growth rates. Between days 30 and 45, the TILs were a mixture of CD3+ CD4+ and CD3+ CD8+ lymphocytes expressing the alpha beta form of the T-cell receptor. TILs derived from each anatomic site specifically lysed autologous tumor obtained from all four anatomic sites. In fine specificity analysis, the TILs exhibited human leukocyte antigen (HLA-A2)-restricted lysis of fresh tumor targets and cultured melanoma cell lines. Each TIL recognized a product of the MART-1 gene, and specifically, the monomer peptide MART-1(27-35). Thus lymphocytes reactive with the MART-1 melanoma antigen appeared to be widely distributed in diverse metastases in this patient. This information, along with previous data on the reactivity of multiple patients to this antigen, attests to its dominance in the immune reactivity of humans to melanoma.
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PMID:Melanoma tumor-infiltrating lymphocytes derived from four distinct anatomic sites obtained from a single patient: comparison of functional reactivity and melanoma antigen recognition. 868 Jun 54

IL-10 is a cytokine which shows various effects including inhibition of T-cell proliferation or HLA-dependent antigen presentation. In this study, we analysed the effects of exogenous or autocrine IL-10 on proliferation and expression of immunocritical surface molecules. Fourteen cultures of human melanoma cells were established from primary melanomas, locoregional lymph-node or distant metastases. In 5 melanoma cell cultures, proliferation in the presence of IL-10, anti-IL-10 antibodies (Ab) or control Ab was assessed with colorimetric and [3H]thymidine uptake assays. Flow cytometric analysis was used to quantify the expression of human leukocyte antigen (HLA) class-I, HLA class-II and intercellular adhesion molecule (ICAM)-1 and the IL-10 receptor (IL-10R). IL-10 production of melanoma cells was documented by RT-PCR and IL-10 protein was detected in the supernatants by means of ELISA. IL-10 enhanced proliferation and prolonged survival of melanoma cells in 5 out of 5 cultures. Anti-IL-10 Ab decreased proliferation. IL-10R expression was found in 12 out of 14 (86%) melanoma cell cultures. The expression of HLA-I, HLA-II and ICAM-1 on all melanoma cells that were positive for IL-10R showed a reduction of 10-60% by IL-10, whereas the surface levels of HLA-I, HLA-II and ICAM-1 in 5 out of 5 cell cultures revealed an increase of 10-170% by anti-IL-10 Ab. These findings suggest that IL-10 is an autocrine growth factor with significant impact on immunocritical molecules in melanoma. IL-10 effects have to be considered when planning therapeutic immunointerventions in melanoma patients.
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PMID:Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules. 917 19

We attempted to correlate the expression of human leukocyte antigen DR (HLA-DR) and tumor infiltration by S-100-protein-positive dendritic cells with clinicopathologic features in 165 patients with gastric cancer. The expression of HLA-DR was correlated with the histologic type. Infiltration of dendritic cells correlated negatively with distant lymph node metastases, clinical stage, and peritoneal invasion. There was no correlation between the expression of HLA-DR and infiltration by dendritic cells. In patients with resectable gastric cancer, the grade of infiltrating dendritic cells may be a suitable predictor of prognosis.
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PMID:Prognostic value of HLA-DR expression and dendritic cell infiltration in gastric cancer. 942 78

Patients with high-risk breast cancer may benefit from dose-escalated chemotherapy. We studied toxicity and therapeutic efficacy of sequential high-dose therapy consisting of two cycles of ifosfamide 12,000 mg/m2, carboplatin 900 mg/m2, and epirubicin 180 mg/m2 (ICE) with peripheral blood stem cell support. Ninety-one patients with advanced breast cancer were included. Fifty-one patients with stage II/III disease and 10 or more tumor-positive axillary lymph nodes received high-dose therapy as adjuvant treatment; the remaining 40 patients were treated for metastatic disease. Peripheral blood stem cells were collected following granulocyte colony-stimulating factor-supported induction chemotherapy. In 68 patients, induction chemotherapy included two cycles of ifosfamide 7,500 mg/m2 and epirubicin 120 mg/m2, while 23 patients received one cycle of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 135 mg/m2, ifosfamide 6,000 mg/m2, and epirubicin 90 mg/m2. One hundred ninety-two cycles of ICE were supported with a median of 3.5 x 10(6) CD34+ cells/kg body weight (range, 1.7 to 38 x 10(6) CD34+ cells/kg body weight), which resulted in rapid hematologic reconstitution with recovery times, for a median neutrophil count of 0.5 x 10(9)/L of 13 days (range, 6 to 20 days) and for a median platelet count greater than 20 x 10(9)L of 9 days (range, 5 to 24 days). Seven patients received only one cycle of ICE because of progressive disease (in two patients with metastatic disease), central nervous system toxicity (one patient), cardiac toxicity (one patient), severe enterocolitis (one patient), development of human leukocyte antigen antibodies (one patient), and wish to withdraw from the study (one patient). Seventeen patients with metastatic disease received an additional high-dose cycle consisting of the non-cross-resistant agents thiotepa 600 mg/m2, etoposide 1,500 mg/m2, and paclitaxel 165 mg/m2. In patients treated adjuvantly, the probability of disease-free survival was 64% at 47 months, which compares favorably with results of conventional treatment protocols, with a 47% event-free probability at the same time period. The probability of progression-free survival in patients with metastatic disease was 18% at 44 months. In conclusion, sequential high-dose therapy with peripheral blood stem cell support in patients with high-risk breast cancer can be administered safely and offers a potential benefit in the adjuvant setting.
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PMID:Efficacy and toxicity of sequential high-dose therapy with peripheral blood stem cell support in patients with high-risk breast cancer. 957 56

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