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)

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

From June 1975 to August 1977, 19 patients with distant metastases of malignant melanoma of the skin that were no longer responsive to chemotherapy were treated with BCG given intravenously. A single dose of lyophilized Pasteur BCG ranging from 2 X 10(7) to 3 X 10(8) viable units was given in 500 ml of saline infused in 5 to 6 h. Seven of the 16 evaluable patients benefited from treatment; 3 showed an objective regression of more than 50% of the original tumor volume, and 4 an arrest of tumor growth. The objective regressions lasted from 2 to 5 months, and 1 case had an arrest of tumor growth for 29 months. The regression rate was related to the BCG dosage: 2 X 10(8) viable units appears to be the dosage that gives severe but reversible toxicity and is able to induce objective regression. The most responsive lesions were skin and subcutaneous deposits (5 of 7) and lung metastases (1 of 4). Toxic effects seem to be related to the number of bacilli injected. In the group of 10 cases treated with less than 10(8) units, toxicity was modest: 4 patients had fever (up to 38.5 degrees C) that lasted a few days, and in 3 cases it was associated with shivering during the infusion period and weakness. One case only had vomiting and jaundice. Toxicity was severe in the 9 patients that were treated with a dosage higher than 10(8): patients had fever and weakness for at least 4 days and shivering during the infusion. Two had adrenal insufficiency and 7 had liver enlargement and jaundice with return to normality by day 21. In the whole series 8 patients had leucopenia and 5 thrombocytopenia for 2 to 3 days: only 1 patient required blood and platelet transfusion. No significant variations in immunoglobulin levels were observed. No variations of PPD or BCG skin tests were observed after treatment. Three patients expired; the first treated with 6 X 10(7) unit, had an intercurrent disease (autopsy showed a heart infarction); the second, treated with 1.8 X 10(8), showed a rapid growth of lung metastases and died 15 days after treatment; the death of the third patient was probably due to anaphylactic shock. All 3 patients had been previously treated with BCG, given by scarification or intranodular injection.
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PMID:Intravenous administration of BCG in advanced melanoma patients. 68 66

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

Spontaneous human lymphocyte-mediated cytotoxicity (SLMC) against tumour-cell targets was examined in a series of patients with localized or malignant disease, both treated and untreated, and patients with untreated chronic lymphocytic leukemia (CLL). The level of SLMC was assessed by means of two previously established assay systems; the xenogeneic assay involving the mouse mastocytoma line P815, and the allogeneic assay in which the human chronic myelogenous leukemia-derived line, K562, was used. The assay systems involve the use of Ficoll-Isopaque-separated, iron-plus-magnetism-purified lymphocytes in an overnight 51chromium release assay, and reflect the cytotoxic ability of human non-T, complement receptor-, Fc receptor-positive lymphocytes. In the present paper, lymphocytes from all normal donors tested showed significant activity in the SLMC assay, with some variation from day to day. This variation was markedly reduced when different normal donors were tested on the same day and under identical experimental conditions. In contrast, lymphocytes from many patients with malignant disease had decreased SLM activity, and this decrease was highly significant in patients with treated or untreated metastatic disease, or untreated CLL. This was also the case when the data were expressed relative to the number of cytotoxic cells in the normal control population, or in comparison to the relative SLMC activity of lymphocytes from patients with other conditions. Markedly decreased SLMC was observed in some patients in spite of normal T and B lymphocyte proportions, or the presence of the ability to mount a vigorous delayed hypersensitivity reaction to PPD. A comparison of the xenogeneic and allogeneic assays showed that the same information with respect to whether SLMC was normal or abnormal was obtained with both assays in the majority of cases. The significance of the data is discussed with respect to the possible role of SLMC in vivo and the relevance of SLMC to the assessment of specific cell-mediated cytotoxicity in malignant disease.
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PMID:Spontaneous human lymphocyte-mediated cytotoxicity againts tumour target cells. I. The effect of malignant disease. 82 77

General immune competence was examined 255 breast cancer patients, including 104 operable, 44 locally advanced/inoperable, and 44 with demonstrable metastatic dissemination, all at the time of diagnosis, as well as 63 disease-free long survivors; this was compared with that of 100 normal controls. The parameters employed were PPD and DNCB skin testing, lymphocyte response to PHA mitogen, E-rosette formation, and lymphocyte number. Significant patients, with only 31% showing optimal and 25% showing minimal levels of immune function, as compared with 70% optimal and 2% minimal function in controls. Immune competence was not affected by metastatic involvement of regional lymph nodes. In patients with early, occult metastatic dissemination (as determined in retrospect), the degree of immune competence was found to be identical to that of patients who did not develop disease dissemination. Remarkably, this early phase of tumor spread is not accompanied by immune impairment, such as is evident in clinically demonstrable metastatic disease and, to a lesser degree, in advanced local and regional disease. Since tumor dissemination preceded impairment of general immunocompetence, it emerges as the cause rather than the result of immunosuppression. Long disease-free survivors, who had postoperative irradiation 5-12 years previously, were shown to have a notably low level of immune competence. Lymphocyte response to PHA stimulation was found to be impaired in the earlier stages of disease, while skin DHR was still well maintained; in advanced disease both parameters tend to correlate as total immunologic impairment ensues. The sequence of immunologic events leading up to immunosuppression with disease progress is discussed.
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PMID:Immunocompetence, immunosuppression, and human breast cancer. I. An analysis of their relationship by known parameters of cell-mediated immunity in well-defined clinical stages of disease. 95 63

In order to evaluate the combination of immunochemotherapy with mitomycin C (MMC), futraful (FT) and PSK, as an adjuvant to surgery for curatively resected gastric cancer, a randomized controlled study by the sealed envelope method was performed with the participation of 97 hospitals in the Kyushu and Chugoku districts of Japan. The MMC + FT + PSK group showed a significant increase in 5 year survival from the other groups (p less than 0.05). Moreover the survival rate was significantly higher in the MMC + FT + PSK group than in the MMC + FT group (p less than 0.01). According to the analysis on stratification, the MMC + FT + PSK group showed the best survival rate in cases with positive lymph node metastases, positive serosal invasion and positive lymph node metastases plus serosal invasion, and in cases of undifferentiated carcinoma by histological type and in those with a preoperative positive PPD reaction (p less than 0.01 or p less than 0.05). Thus, the combination of MMC, FT and PSK was indicated to be useful as an adjuvant immunochemotherapy for those patients with gastric cancer submitted to curative resection.
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PMID:Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years. 315 19

The effects of human osteosarcoma (OS)-specific dialyzable leukocyte extracts (DLE) in hamsters bearing human OS were investigated. The DLE used in this investigation was prepared from rabbits immunized with human osteosarcoma-associated antigens (DLE-OSAA). Tuberculin (DLE-PPD) and control DLE were prepared from rabbits injected with tuberculin or 0.85% NaCl (DLE-NaCl). DLE was administered subcutaneously into inbred hamsters (each injection contained DLE derived from 10(7) rabbit leukocytes). Four groups of animals were studied: group 1, amputation alone; group 2, amputation plus DLE-OSAA; group 3, amputation plus DLE-PPD; group 4, amputation plus DLE-NaCl. Of the DLE-OSAA-treated animals (group 2), 60% were still alive at 300 days postamputation; whereas in animals in groups 1, 3, and 4, all died within 90 days postamputation. In separate experiments, we found that 100% of the animals in groups 1, 3, and 4 developed pulmonary metastases within 30-60 days postamputation, whereas only 20% of the animals in group 2 developed metastases at the same time; indeed 40% of the DLE-OSAA-treated animals were free of metastases in 240-300 days postamputation. Both the leukocyte adherence inhibition assay (LAI) and lymphocyte DNA synthesis assay (LDS) were used to monitor the transfer of antigen-specific cell-mediated immunity in each group of tumor-bearing hamsters. All surviving hamsters in group 2 had high LAI and LDS activity. Our results suggest that DLE-OSAA is effective in preventing pulmonary metastases and death of OS-bearing hamsters (after amputation) as compared with amputation alone, amputation plus DLE-NaCl, and amputation plus DLE-PPD, and that its effect is via an antigen-specific mechanism.
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PMID:An animal model for evaluation of antigen-specific dialyzable leukocyte extracts therapy of osteosarcoma. 347 Jan 62

A multiparametric observation of cellular immune status by delayed hypersensitivity response to primary and recall antigens, absolute lymphocyte counts, T-cells counts, lymphocyte stimulation to PHA and serum immunoglobulin levels (IgG, IgM, IgA) was done in 60 patients of breast cancer and 40 age-matched normal controls. The findings were correlated with clinical stage, tumour size, lymphnode involvement, distant metastases, tumour differentiation, lymphoreticular response and tumour recurrence within one year of follow-up period. Delayed hypersensitivity response to DNCB, PPD and Candida was significantly impaired (P = less than .001) in breast cancer patients as compared to normal controls. DNCB and candida response showed a gradual decrease with increasing clinical stage and PPD response was impaired in the advanced stage (Stage III and IV). Patients with well-differentiated tumour were more anergic than those with poorly differentiated tumour. Delayed hypersensitivity response to both primary and recall antigen showed a good correlation with tumour recurrence. Patients who had early recurrence or progressive disease were more anergic to all the three antigens. Absolute lymphocyte counts, absolute T-cells and E-rosette were significantly reduced in breast cancer patients as compared to normal controls and further correlated with clinical stage. Absolute T-cells and E-rosettes were lower in patients with lymphnode involvement, and distant metastases as compared to those with localized tumour. Absence of lymphoreticular response was related with impaired T-cell population. Absolute T-cell counts and E-rosettes further correlated with prognosis of the patients being significantly impaired in patients with early recurrence or with progressive disease (P = less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A multiparametric observation of immune competence in breast cancer and its correlation with tumour load and prognosis. 387 55

The anti-tumor effect of immunization with heat-killed Mycobacterium tuberculosis (Tbc) and Tuberculin (PPD)-coupled syngeneic tumor cells was examined in vivo. Three tumor cell lines were employed. Immunization of Tbc-primed BALB/c mice with PPD-coupled syngeneic Meth-A tumor cells displayed a potent anti-tumor effect on viable Meth-A cells inoculated subcutaneously. Neither PPD-coupled LLC (Lewis Lung Carcinoma) cells nor sonicated PPD-coupled Meth-A cells were capable of immunizing these mice. PPD-coupled syngeneic whole tumor cells were indispensable for induction of this tumor-specific resistance. Immunization of Tbc-primed C3H/He mice with PPD-coupled syngeneic MH134 tumor cells did not elicit anti-tumor activity against MH134, but additional pretreatment of mice with cyclophosphamide brought on an anti-tumor effect. Antimetastatic reactivity was investigated in C57BL/6 mice bearing LLC, with a reduction in metastases noted. This antimetastatic effect was observed even when the mice were immunized with PPD-coupled LLC cells three days after removal of the initial tumor. Immunization with Tbc and PPD-coupled Meth-A cells together with intraperitoneal administration of murine or rat interleukin 2 (IL 2) further augmented anti-Meth-A resistance. Murine IL 2 further inhibited tumor growth during the early stage, while rat IL 2 showed an anti-tumor effect throughout the course of tumor growth.
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PMID:Augmentation of anti-tumor activity by immunization with Mycobacterium tuberculosis (Tbc) and tuberculin-coupled tumor cells. 392 81


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