Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MHC class I antigens participate in the immune response by presenting peptides to CD8+ cytotoxic T cells. Decreased expression of these antigens in tumor cells may contribute to an evasion of immune system and consequently to enhanced tumor growth. However, not all tumors expressing low levels of HLA antigens show increased malignancy, probably as a result of the differential activity of the oncogenes involved in malignant transformation. The ras family of cellular oncogenes is one of the most frequently detected families of transformation-inducing genes in human solid tumors. The aim of this work is to study the expression of MHC antigens and the ras oncogene product, p21ras, in 60 primary breast tumors in order to define its clinical significance in tumor progression. HLA antigen expression and p21ras levels were measured on breast tumors using immunohistochemistry methods and enzymoimmunoassay, respectively. The results demonstrate that more invasive tumors have both a decreased expression of HLA class I antigens and higher levels of p21ras protein expression than less aggressive tumors. These findings indicate that the capacity of breast cancers to grow and metastasize is related to low levels of MHC class I antigens and enhanced p21ras expression, thus supporting the involvement of MHC and ras oncogenes in breast tumor malignancy.
Invasion Metastasis 1992
PMID:MHC class I antigen expression is inversely related with tumor malignancy and ras oncogene product (p21ras) levels in human breast tumors. 129 32

This study reports on biological response modification induced by prolonged continuous subcutaneous (s.c.) infusion of recombinant interferon-gamma (rIFN-gamma) with particular attention to changes of soluble CD14. This glycoprotein with an unknown function is derived from myeloid cells carrying membrane CD14, which is the receptor for lipopolysaccharide (LPS)-LPS-binding protein (LBP) complexes. Fifteen metastatic cancer patients received weekly escalating doses of rIFN-gamma starting at either 50 or 100 micrograms/24 h and increasing up to 400 micrograms/24 h for a median duration of 6 weeks. The maximum tolerated dose was higher (200 micrograms/24 h) with the lower (50 micrograms/24 h) starting dose. Biological activity of rIFN-gamma was evaluated by weekly measurements of CD14, neopterin, and beta 2-microglobulin concentrations in serum as well as monocyte HLA class I and II antigen expression and tumor cytotoxicity. Serum IFN-gamma concentrations increased 20-fold within 4 weeks of therapy. The levels were correlated to the mean dose (r = 0.95, p less than 0.05). Among the biological markers, two patterns were observed. First, serum CD14 concentration and expression of monocyte HLA class II antigens increased significantly during the first week, and marker expression correlated with serum IFN-gamma levels (p less than 0.05); CD14 and HLA class II antigens thereafter returned to pretreatment levels within 4 weeks of therapy despite persistently elevated serum IFN-gamma concentrations. Second, serum neopterin and beta 2-microglobulin concentrations as well as monocyte HLA class I expression also increased significantly within the first week, but remained elevated thereafter without any further dose relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prolonged interferon-gamma application by subcutaneous infusion in cancer patients: differential response of serum CD14, neopterin, and monocyte HLA class I and II antigens. 137 54

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

Human leukocyte antigen (HLA) classes I and II molecules are essential for antigen presentation to cytotoxic T cells and helper T cells, respectively. Consequently, they may play a role in anticancer immunotherapy as well. We studied whether the pretreatment HLA phenotype of the tumor is predictive for response to interferon immunotherapy in vivo. Therefore, renal cell carcinoma (RCC) primary tumor lesions from 31 patients treated with interferon-alpha and interferon-gamma (13 responders and 18 nonresponders) were analyzed retrospectively for HLA antigen expression with immunohistochemical methods. Furthermore, from eight patients, pretreatment metastatic lesions were examined. In the primary tumors HLA class I expression was high: in 26 of 30 lesions more than 50% cells were stained. HLA class II expression was mostly low: in 14 of 31 primary tumors less than 5% cells were stained. A significant correlation was found between HLA phenotype of primary tumors and corresponding metastases. There was no association between tumor HLA classes I and II antigen expression and clinical response to interferon therapy. In conclusion, pretreatment HLA phenotype of RCC has no predictive value for outcome of interferon immunotherapy. A role for treatment-induced changes in HLA expression in vivo, however, can not be excluded. These findings do not provide indications for the working mechanism of interferon immunotherapy in vivo.
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PMID:Human leukocyte antigen expression in renal cell carcinoma lesions does not predict the response to interferon therapy. 163 84

The distribution of MHC antigens in human melanocytic lesions, i.e. HLA class I and HLA class II antigens is reviewed. HLA class I antigens have a broad distribution, but may be lost during tumor progression. In contrast, HLA class II antigen expression appears with neoplastic transformation. The mode of regulation of HLA antigens in melanoma lesions is complex. Immunohistochemical demonstration of HLA antigen expression in primary melanoma lesions and in locoregional metastases has prognostic relevance. Expression of HLA-DR in primary melanoma lesions is associated with an unfavorable prognosis, as is a decreased expression of HLA-A,B,C antigens in locoregional metastases.
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PMID:MHC antigens in human melanomas. 191 17

1. Survival of skin allografts in mice is increased in proportion to the duration of anaesthesia to a degree that is equivalent to that achievable with a major immunosuppressive agent such as azothiaprine or antilymphocyte serum. 2. Immune cytochemical studies have demonstrated that bladder tumors which metastases express beta HCG and show variable degrees of loss of HLA class I antigens--features which mimic the behaviour of human trophoblast in protecting the foetus from maternal rejection. It is concluded that there may be a case for using such prognostic factors to define a sub group of patients in whom reconstruction of the bladder following cystectomy should be deferred until the patient has survived without metastases for a prolonged period.
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PMID:Operative factors & tumor membrane antigen changes in escape from immune surveillance of bladder cancer. 192 47

The expression of monomorphic determinants of the histocompatibility leukocyte antigens (HLA) class I antigens by human malignant tumor cells was studied in tissue specimens of 70 primary tumor lesions obtained from patients with carcinoma of the breast (41 patients), colon (8 patients), urinary bladder (8 patients), and kidney (13 patients), and in samples of either synchronous or metachronous lymph node, lung, or liver metastases available in 44 of the patients. The frequencies of HLA class I expressor and nonexpressor tumor cells were determined by immunohistochemical staining of histological sections of fresh frozen tissue samples with the W6/32 monoclonal antibody. The tumor cell populations in the majority of the primary lesions consisted predominantly of HLA-immunoreactive cells (observed in 38 of 70 patients; 54%), especially in those patients who did not have clinical evidence of metastatic disease (8 of 11 patients; 73%). Various degrees of loss of reactivity were observed in other primary lesions, although in only 8 (12%) tumors (7 of which were obtained from patients with metastatic disease), the neoplastic cells were nearly exclusively HLA-nonreactive. In contrast, the majority of metastatic lesions consisted of either predominantly HLA-negative cells (33 of 44 specimens; 75%) or mixed populations (10 of 44 specimens; 23%), whereas only one metastatic lesion manifested HLA class I antigen staining in more than 70% of its tumor cells (P = 0.0005). Intravascular clusters of tumor cells consisted predominantly of HLA class I nonexpressors. The observed patterns of distribution of HLA expressors and nonexpressor tumor cells are compatible with the notion that HLA-negative cells in human carcinomas manifest a selective advantage with regard to metastatic progression and growth. The suppressed expression of major histocompatibility complex class I antigens on metastatic cells may lead to failure of presentation of cell surface tumor specific epitopes to host cytotoxic T-lymphocytes. Such a process would enable tumor cells to evade host immune responses and would promote and enhance cell dissemination and metastatic growth.
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PMID:Expression of HLA-A,B,C antigens on primary and metastatic tumor cell populations of human carcinomas. 193

A series of 60 primary laryngeal and hypopharyngeal tumours, 24 lymph node metastases and normal tissue were evaluated in frozen sections for the expression of MHC class I antigens, using monoclonal antibodies. We found 13 cases presenting total HLA-ABC losses, 5 selective losses of HLA-A antigens and 1 of HLA-B antigens. We were able to find statistical association between these losses and a number of clinical and pathological parameters, such as T and N stage, degree of differentiation, scores according to Jakobsson and Glanz grading systems, vascular invasion or leukocytic infiltrate. Our results lead us to the following conclusions: a) HLA class I losses were found in a group of tumours showing a greater aggressiveness and worse prognosis; b) these alterations in the expression are not associated with a increased metastatic potential. Thus, the absence of HLA molecules in laryngeal tumours is related to a greater local aggressiveness, and the loss of class I antigens seems to constitute and adaptive tumour mechanism to avoid the different anatomical and immunological barriers present in the laryngeal organ.
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PMID:[Immunologic modulation of tumor aggressiveness in cancer of the larynx. II. Clinicopathologic correlations with the loss of expression of the HLA ABC antigens]. 209 25

Swainsonine, an indolizidine alkaloid, can decrease the organ colonization potential of metastatic murine tumor cells by augmentation of host immune effector mechanisms. In this report the above findings were extended by the demonstration that systemic administration of swainsonine strongly suppressed the growth of human breast carcinoma subcutaneous xenografts and experimentally induced lung metastases. This inhibition was not due to a direct effect of swainsonine on cell growth. However swainsonine treatment of tumor cells resulted in enhanced expression of HLA Class I antigens, and HLA class I mRNA. Swainsonine was a potent immunodulator as evidenced by the increased (a) cytotoxicity of splenocytes and macrophages, and, (b) proliferative potential of splenocytes and bone marrow cells. These data suggest that swainsonine-induced inhibition of tumor growth and metastases may be mediated via activation of host effector cells and/or alteration of tumor cell antigenicity.
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PMID:Inhibition of growth of subcutaneous xenografts and metastasis of human breast carcinoma by swainsonine: modulation of tumor cell HLA class I antigens and host immune effector mechanisms. 212 82

A series of 60 primary laryngeal and hypopharyngeal tumours, 24 lymph node metastases and normal tissue were evaluated in frozen sections for the expression of MHC class I antigens, using monoclonal antibodies and the APAAP technique. We found 13 tumours presenting total HLA-ABC loss, five with selective loss of HLA-A antigens and one with absence of HLA-B antigens. These losses were statistically associated with clinical and pathological parameters, such as T stage, degree of differentiation, scores according to the Jakobsson and Glanz grading systems and degree of leukocytic infiltration. Our results lead us to the following conclusions: (a) HLA class I losses were found in a group of tumours showing greater aggressiveness and worse prognosis; (b) these alterations in expression were not associated with an increased metastatic potential. Thus, the absence of HLA molecules in laryngeal tumours is related to greater local aggressiveness, and the loss of class I antigens seems to constitute an adaptive tumour mechanism to avoid the different anatomical and immunological barriers within the larynx.
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PMID:Lack of MHC class I antigens and tumour aggressiveness of the squamous cell carcinoma of the larynx. 225 12


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