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)

A macroglycoferroprotein of hepatic orgin, alpah2H globulin, the serum level of which increases a few weeks or months before local recurrence of metastases, has been essayed for its immunosuppressive activity. The study was carried out using the lymphoblastic transformation test and was judged by tritiated thymidine incorporation and microscopic examination. PHA-induced blast transformation of 97 per cent of normal donor lymphocytes is inhibited by 100 mug/ml of alpha2H globulin. This inhibitory effect is proportional to the quantity of added alpha2H globulin. In is obvious with a concentration of 2-5 mug/ml, a frequently observed level in the serum of patient with tumours. Preincubation of lymphocytes with alpha2H globulin renders more effective the inhibitory action on PHA-induced transformation. A mechanism of competition between PHA and alpha2H globulin is suggested by preincubation and the inhibitory effect related to the doses. However, microscopic observation shows that alpha2H globulin acts on the earliest events occurring to the stimulated lymphocytes, by inhibiting cytoplasmic RNA and protein synthesis. The alpha2H globulin effect may not only have an immunosuppresive activity but it may have a more general effect, for example blocking or modifying cellular respiration.
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PMID:Immunosuppresive effect of a human hepatic glycoferroprotein, alpha2H globulin. A study on the transformation of normal human lymphocytes. 4 95

The immune responses of 60 patients undergoing therapeutic irradiation were evaluated according to four anatomical sites irradiated. In vitro lymphocyte transformation tests with PHA, Con-A, and PWM and quantitative assays of IgG, IgA, and IgM were performed on blood obtained from each patient before and during therapy, and two weeks, two months, and six months after therapy. At these same testing intervals, skin tests with PPD, mumps antigen, Candida antigen, and SD-SK were performed. During irradiation, the mean values of all lymphocyte transformation tests were depressed, varying from 48% to 64% of pretreatment baseline. This depression persisted until about two months after completion of treatment. By six months, response rose to pretreatment values. When response was evaluated according to sites irradiated with all mitogens, the pelvic and pelvic plus abdominal groups showed consistently greater depression than the chest or head and neck groups. Radiation effected no significant changes in the mean values of IgG, IgA or IgM. A decrease in skin sensitivity was noted during radiation; 73% of the subjects responded positively before therapy while only 53% had at least one positive test during therapy. By two months postirradiation, 73% of the group clinically free of disease had positive skin tests. A comparison of clinical condition with test results is significant when one considers the 17 patients who developed metastatic disease or died from disease. The depression for all three mitogens during radiation therapy was greater for this group. Of the 17, only four had IgG levels in the normal range, and consistently fewer positive skin tests were demonstrated.
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PMID:Effect of therapeutic irradiation on the immune responses. 17

The clinical findings in 262 patients with melanoma were correlated with an assessment of their cellular-mediated immunity by delayed-type hypersensitivity (DTH) skin tests, by lymphocyte blastogenesis, and by leukocyte enumerations. Patients with systemic metastases (stage IV) and those with evidence of tumor burden had fewer positive DTH reactions for recall antigens than did patients with localized disease (stage I), patients with no evidence of tumor burden, and 227 normal controls. However, no differences were found in the magnitude of response among patients with melanoma or when compared with controls. Patients with melanoma had fewer responses to dinitrochlorobenzene (40% than did controls (98%), but there were no differences by stage or tumor burden. Similarly, blastogenesis in the presence of PHA, Con A, and PWM was depressed when compared with controls, but there was no meaningful correlation with the clinical status. Leukocyte, T cell, or B cell counts revealed no alteration from normal for the patients with melanoma. The usefulness of these studies for routine clinical monitoring is questioned.
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PMID:A prospective study of immune responsiveness in human melanoma. I. Assessment of initial pretreatment status with stage of disease. 30 70

Children with localized and metastatic neuroblastoma were studies to determine their immune status at the time of diagnosis and while they were receiving intensive intermittent chemotherapy; Investigations included leukocyte and differential counts, delayed hypersensitivity response, quantitative serum immunoglobulins, percentages of T and Fc receptor lymphocytes, PHA-induced mitogenesis, and antibody-and PHA-dependent cellular cytoxicity. Abnormalities related to the neoplasm at diagnosis were limited to depressed leukocyte and lymphocyte counts and increased concentrations of serum IgM in patients with metastases to bone marrow and other sites. No abnormalities were observed in those with localized tumors. Intermittent chemotherapy of metastatic neuroblastoma caused immunosuppression. Effects were most marked during five-day courses of chemotherapy; they included abrogation of DH and decreased leukocyte and lymphocyte counts and percentages of Fc receptor lymphocytes. Recovery of DH with partial recovery of leukocyte and lymphocyte counts was observed three weeks, later, prior to the next course, We conclude that both metastatic tumor and chemotherapy cause abnormalities of the immune system in children with neuroblastoma.
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PMID:Abnormalities of the immune system in children with neuroblastoma related to the neoplasm and chemotherapy. 32 Feb 98

We have previously shown that soluble extracts from human colonic carcinoma (SCE) were potent inhibitors of the PHA-induced DNA synthesis of normal allogeneic peripheral lymphocytes. From the present study, SCE appeared to have a broad and nonspecific range of activity. The SCE-suppressive effect was observed whatever the lymphoid organ or the animal species used as a source of stimulated lymphocytes. Moreover, we always obtained a complete inhibition of the lymphoproliferative response to all tested mitogens including PHA, Con A, PWM, and, for animal lymphocytes, LPS. In addition to the suppressive activity on lymphocytes, SCE also inhibited proliferation of cultured human CCL6 embryonic intestine cells and HT29 colonic carcinoma cells, and of cultured rat fibrosarcoma cells. Soluble extracts from HT29 cells (SCCE) were able to mimic the nonspecific suppressive and cytostatic activities of SCE. The suppressive activity was also found in extracts from hepatic metastases (SHME) of a primary colonic tumor. In contrast, soluble extracts from normal liver or nonmalignant colonic mucosa did not interfere with cell proliferation. These data suggest that both SCE and SCCE contain molecular components(s) that can inhibit a wide variety of proliferating cells, including stimulated lymphocytes.
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PMID:Nonspecific suppressive and cytostatic activities mediated by human colonic carcinoma tissue or cultured cell extract. 67 Jul 7

We have examined 111 cancer patients and 111 control individuals for general immunocompetence (haematological values, "recall" antigen skin tests, PHA and PPD induced lymphocyte transformation, serum Ig levels and lymphocyte subpopulations), for evidence of sensitisation to tumour-associated antigens (leucocyte migration test, serum inhibition of autologous leucocyte migration, lymphocytotoxicity, membrane immunofluorescence and immune adherence) and for evidence of continuing immune reactions (alterations of complement components and anticomplementary activity). Major differences between the cancer patients and controls were demonstrated by several tests of sensitisation and these also detected differences between patients with and without metastases. The only differences detected between cancer patients and controls by the tests of general immunocompetence were in serum IgG and IgA (higher in the cancer patients) and lymphocyte subpopulations ("active" T, autorosetting lymphocytes and lymphocytes forming "super-rosettes" increased in cancer patients). In a comparison of cancer patients with and without metastases, patients with metastases were less often reactive to the Candida DHS and streptokinase-streptodornase antigens and had raised circulating Fc positive cells. Abnormalities of the individual components of complement occurred in about half the cancer patients, but were equally common in those with and without metastases. Serum anti-complementary activity was very rarely detected. The tests of specific sensitisation correlated reasonably well but correlations of tests of general immunocompetence were infrequent.
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PMID:An examination of the immunology of cancer patients. 78 52

This study assess the effects of oral BCG, as a single agent, on tumor progression and on cell-mediated immune function in patients with metastatic malignant melanoma. Thirty patients were studied including 22 with measurable metastatic lesions and 8 with no detectable disease, following treatment of metastases by surgery, radiotherapy, or 5-(3, 3-dimethyl-1 -triazeno)-imidazole-4-carboxamide (DTIC; DIC). Oral BCG was given in doses of 120--240 mg, 1--3 times per week for periods ranging from 9 to 80 weeks and to total doses of from 1.2 to 20.1 gm. Patients were assessed by direct measurements of tumor mass, PPD skin test and in vitro blastogenic responses to PPD PHA. Of the 22 patient with measureable disease, 19 showed tumor progression and none showed regression of any lesion. Of the 8 without apparent disease, 5 remained stable and 3 had tumor recurrence. Of the total group of 30 patients, 8 showed some increased sensitivity to skin testing with PPD. Of 19 tested, 3 showed an increased PPD response in vitro, while 3 showed a decreased response. Six of 20 tested showed an increased PHA response in vitro. Oral BCG alone was not effective as an antitumor agent in patients with metastatic malignant melanoma.
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PMID:The use of oral BCG in the treatment or metastatic malignant melanoma. 78 99

Immunocompetence and prognosis are related in solid tumors, malignant lymphomas, and acute leukemia. Among the parameters of immunocompetence vigorous delayed-type hypersensitivity responses to recall antigens or to primary immunization with Keyhole limpet hemocyanin, vigorous in vitro lymphocyte blastogenic responses to mitogens such as PHA, and relatively high B-lymphocyte levels, all correlate with a good prognosis. The spectrum of immune reactivity as measured by established delayed-type hypersensitivity to recall antigens and in vitro blastogenic responses to mitogens and antigens is similar in melanoma patients and their nontumor-bearing spouses. In melanoma, only patients with widespread inoperable metastatic disease show severe immunological deficiency and this is selective for certain antigens. There are highly significant differences in response to specific antigens when patients with melanoma and lung cancer are compared. Immunotherapy with BCG and C. parvum can boost immunocompetence as measured by recall DTH skin testing. However, the relationship between the initial immunocompetence and prognosis still holds in patients receiving BCG immunotherapy to prevent recurrence of melanoma. These data indicate that a broader survey of immunological reactivity in cancer patients is needed, that immunological testing is useful in cancer prognosis clinically, and that the results of immunological testing can be used to evaluate therapy and to indicate new pathways for improved treatment.
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PMID:Immunocompetence, immunodeficiency and prognosis in cancer. 80 Mar 24

Fifty-one patients with advanced lung cancer were divided at random into two groups. One group of 29 patients received the methanol extraction residue (MER) of Bacille-Calmette-Guerin (BCG) in addition to radiotherapy and/or chemotherapy. The other group of 22 patients was treated by radiotherapy and/or chemotherapy alone. The immune status of the patients was evaluated by skin tests to three recall antigens and KLH and by in vitro lymphocyte stimulation to PHA and three recall antigens. The immune status of both groups was similar before and after conventional treatment. The cutaneous reactivity, as well as the in vitro lymphocyte reactivity, became stronger in the MER-treated group, as compared with the control group. The MER-treated patients had less distant metastases. In a comparable clinical stage the survival in the MER treated group was slightly but not significantly better. This study has shown that MER stimulates the immune response, can be well tolerated and has few side effects. Therefore, MER treatment of patients with minimal tumor load can ethically be done with hope of obtaining better results.
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PMID:Treatment of lung cancer by radiotherapy, chemotherapy, and methanol extraction residue of BCG (MER): clinical and immunological studies. 90 32

The mononuclear cell content and mononuclear cell function of human solid tumors were determined. Twenty-eight primary, and 17 metastatic solid tumors, including 6 lymph node metastases, were obtained from 45 patients. Cells were released from the tumors by mincing, scraping, and sieving. Analysis of the cellular content was determined by light microscopy, and tumor lymphocyte function was determined by stimulation of blastogenesis with PHA, PWM, Con-A, MLC, and SLO. A median of 3.3 X 10(7) tumor cells with 12.5% viability was obtained per gram of tumor, and a median of 7.8 X 10(6) lymphocytes with a viability of 96% and 0.35 X 10(6) macrophages with a viability of 85% was also obtained per gram of tumor. Significant lymphocyte responses to various mitogens and antigens were obtained in 31-40% of the tumor lymphocyte preparations. From 9.4% to 23% had vigorous responses with a stimulation index greater than 10. Primary tumors contained significantly more lymphocytes than metastatic tumors; thus, the percent lymphocytes in primary tumors was 13.5% compared to 5% for metastatic tumors. In contrast, some of the lymphocyte responses were significantly greater for metastatic tumors than primary tumors. These data suggest that the direct study of lymphocytes infiltrating primary and metastatic tumors may be a useful approach to understanding tumor immunity in man.
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PMID:Mononuclear cell content of human solid tumors. 93 26


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