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 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 authors present the results of investigations of the immune reactivity of 72 patients irradiated for testicle tumors. The responses to tuberculin and DNCB (2.4-dinitrochlorobenzol) were examined before the treatment, within twelve months after radiotherapy and three years after radiotherapy and when metastases appeared. After radiotherapy, the number of positive responses was slightly decreased in both examination methods, but the difference was in no case significant. Patients with metastases showed a significantly decreased response to DNCB compared to the results obtained before radiotherapy. 5.6% of the patients had suffered from herpes zoster. The incidence of other infective diseases was not increased. The conclusion is drawn that the moderate immunosuppression caused by radiotherapy does not exert any influence on the further way of living of patients with testicle tumors.
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PMID:[The immune status of patients with irradiated testicular neoplasms]. 402 64

A new bleomycin derivative NK631 was administered in five cases of advanced recurrent oral carcinoma. The visible improvement of the tumor was noted in three cases, and in the cases of lower lip carcinoma the tumor completely disappeared, however, there was no effective change in cases of cervical metastases of the floor of the mouth and tongue carcinoma. The peripheral lymphocyte counts and serum proteins disclosed a characteristic decrease, serum proteins decreased in the albumin fraction and slightly increased in alpha 2-globlin fraction. Main side effects of NK 631 were skin exanthema, alopecia, anorexia, pyrexia, fatigue and bleeding from the tumor lesion. Regarding the lung function, the vital capacity did not change, but PaO and PaCO in blood gas analysis were together observed to slightly decrease, and it may be supposed that the influence of NK631 on the lung function cannot be neglected. T-cell ratio, lymphocyte blastoformation following PHA stimulation, PPD and DNCB skin tests, and phagocytosis test of peripheral leucocytes were studied. The immuno-suppressive effect of KK631 was the same or weak as bleomycin.
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PMID:Effect of a bleomycin derivative on oral carcinoma. A clinical and immunologic study of five cases. 615 49

A total of 50 patients with primary malignant melanomas received epifocal DNCB therapy. In 46 cases the tumors disappeared completely. Therefore, we partly refrained from excision of the treated area. Only 4 melanomas of great thickness did not respond satisfactorily. In the treatment of cutaneous metastases, however, remission was achieved only in one case. The 5-year survival rate for primary tumors was 87.8 +/- 10.55%. We believe that DNCB therapy is indicated especially in superficially growing melanomas, patients with limited operability, or flat melanomas of acral localization, where the patients are spared mutilating operations.
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PMID:Epifocal dinitrochlorobenzene therapy in malignant melanoma (experience during the last eight years). 648 34

Although cyclophosphamide (CY) is a potent immunosuppressive drug, under the proper conditions, it can potentiate immune responses as well. In past work, we have shown that administration of a commonly used oncostatic dose of CY (1000 mg/sq m) to patients with advanced cancer 3 days before sensitization with the primary antigen, keyhole limpet hemocyanin (KLH), resulted in augmentation of delayed-type hypersensitivity (DTH) but not antibody response to that antigen. The present study was performed to test the immunopotentiation of a lower dose of CY (300 mg/sq m); animal studies and studies of human lymphocytes in vitro suggested that the lower dose might be more effective. Eighteen patients with advanced metastatic cancer were alternately assigned to one of two groups. Sixteen days before CY, one group received KLH and the other group received 1-chloro-2,4-dinitrobenzene (DNCB). CY 300 mg/sq m was given as an i.v. bolus on Day 0. Three days after CY, the patients received KLH or DNCB, whichever they had not received initially. Blood was drawn for antibody titer, and skin testing was performed 14 days after administration of KLH or DNCB. In addition, skin tests to microbial recall antigens were made 2 days before and 17 days after CY. Pretreatment with low-dose CY resulted in significant augmentation of DTH to KLH; thus, the median DTH responses were: KLH alone, 10 mm; and KLH after CY, 27 mm (p less than 0.01). CY pretreatment also resulted in augmentation of the antibody response to KLH. The median total antibody titers (log2 of reciprocal of dilution) were as follows: KLH alone, less than 1; and KLH after CY, 3 (p less than 0.01). All nine CY-pretreated subjects but only 4 of 9 controls developed measurable anti-KLH antibody titers. CY pretreatment neither augmented nor suppressed the 48-hr challenge reaction to DNCB. Moreover, CY had no effect on DTH responses to the recall antigens, dermatophytin, Candida, and mumps.
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PMID:Potentiation of human cell-mediated and humoral immunity by low-dose cyclophosphamide. 648 95

40 patients with benign paraproteinemia have been studied in relation to their age and associated diseases. Significantly high frequency of liver diseases (CALD, cirrhosis, hepatoma, metastases) has been found (12 over 40 people) and increased incidence of idiopathic paraproteinaemia in the old age has been confirmed. 9 patients have been followed for 5 years, so that one could be sure that they had really benign paraproteinaemia: these patients have been then studied from an immunological point of view, in vivo by means of skin tests (PPD, Candida, Trichophyton, DNCB) and in vitro by searching for circulating immune complexes (using a new highly specific immuno-enzymatic method), and compared to controls without paraproteinaemia. Highly positive skin tests have been found only in 7 over 9 patients (even in old subjects) and 6 of them had circulating immune complexes (C.I.C.) in their sera; all the controls were negative both for skin tests and for C.I.C. Immune complexes have been found also in some cases of idiopathic paraproteinaemia, so that they do not seem to be in relation to the associated diseases. The Authors suggest that a genetically determined defect in regulator/suppressor T lymphocyte activity may cause the growth of a benign B cell neoplasm; and that monoclonal immunoglobulins most probably have antibody specificity and are directed against target antigens.
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PMID:[Benign monoclonal gammopathies: probable antibody specificity of monoclonal immunoglobulins]. 664 78

The aim of this study was to investigate the compound 4-nitro-1-cyclohexyl-3-ethoxy-2-oxo-3-pyrroline (NOPYE) and some related compounds for skin sensitization in guinea pigs, as the first step in a search for more effective skin sensitizers for immunotherapy of cutaneous tumors. In guinea pigs, NOPYE and NOPYE-L-alanine produce far milder delayed hypersensitivity reactions than DNCB. Both NOPYE and DNCB fail to act as adjuvants for skin sensitization to tuberculin purified protein derivative (PPD) and ovalbumin (OV). This suggests an explanation for the lack of effectiveness of DNCB in immunotherapy of metastases: DNCB may be relatively ineffective as an adjuvant for production of specific antitumor immunity. Such adjuvant activity may be essential if the action of the immunotherapeutic reagent is not to be confined to its site of application but is to be effective at the site of distant metastases.
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PMID:Skin sensitization with the new reagents NOPYE (4-nitro-1-cyclohexyl-3-ethoxy-2-oxo-3-pyrroline) and NOPY-L-phenylalanine. 735 20

Comprehensive immune function by integrated score was assessed in 158 operable, 55 inoperable, and 52 metastatic breast cancer patients relative to 107 healthy controls. The score was derived from in vivo response to PPD and DNCB and in vitro lymphocyte stimulation by PPD and PHA. Proportion of E-RFC was significantly lower in patients than in controls but was not found to correlate directly with the above functional criteria. Fifty-one percent of the patients with early, operable tumors were shown to be at least partially immunosuppressed by integrated score achievement vs. 11% of controls. This proportion rises to 68% of inoperable and 89% of metastatic patients. Quantitative analysis by graded response revealed an additional, significant degree of immune impairment in the respective patient groups by all testing parameters. Depression of immune function in operable patients was not related to age nor influenced by surgery. Immunocompetence of patients with mammary dysplasia did not differ from controls. Increasing size of primary tumor (T) was not found to be matched by progressive degree of immunosuppression, excepting that associated with large T4 tumors. Patients with lymph node involvement (N+) were not significantly immunologically inferior to those without (N0) where the larger operable T2-3) tumors are concerned. In the smallest, T1 tumors, nodal involvement (N+) is accompanied by remarkable immunosuppression relative to T1N0 cases. This finding suggests a pre-existing immune defect inherent in T1N+ patients. It supports the hypothesis that the immunosuppression associated with early breast cancer is primary, patient related. Secondary tumor-induced depression of immune response characterizes advanced and metastatic human breast cancer.
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PMID:Immunocompetence, immunosuppression, and human breast cancer. II. Further evidence of initial immune impairment by integrated assessment effect of nodal involvement (N) and of primary tumor size (T). 737 Sep 52

The prognostic significance of immunocompetence determined at diagnosis was analyzed in 158 operable breast cancer patients followed for 3--6 years, in terms of disease recurrence and of length of disease-free period (DFP) and in 52 patients with metastatic disease in terms of length of survival. In vitro lymphocyte stimulation by PPD and PHA were of higher predictive value with respect to probability of disease recurrence than in vivo cutaneous reactivity to PPD and DNCB. Conversely, length of DFP and of survival were found to correlate better with in vivo than within vitro parameters. Absolute number of peripheral blood lymphocytes (PBL) and percent of E-rosette-forming cells (E-RFC) proved devoid of prognostic value. Prognostic separation was best brought out upon analysis by integrated score of immunocompetence, comprising the four functional parameters. Probability of disease recurrence was 0.43 for all operable patients, as calculated by actuarial method 48 months postoperatively; it was 0.26 for optimal and 0.61 for suboptimal responders (P less than 0.0001). Separate analysis of Stage 1 (N0) and Stage II (N+) patients revealed prognostic segregation within each stage: probability of recurrence in Stage I was 0.06 for optimal vs. 0.41 for suboptimal responders (P less than 0.001) and in Stage II it was 0.45 vs. 0.79, respectively (P less than 0.01). These findings may prove valuable for a more selective patient allocation for post-mastectomy adjuvant therapy. Length of DFP was found inversely proportional to initial immunocompetence, with a mean of 23.5 months for good responders and 12.8 months for poor responders (P less than 0.01). Length of survival of metastatic patients was found to correlate with initial (pretreatment) levels of immunocompetence, mean survival being 29.5 months for those with preserved immune function and 12.3 months for the immunosuppressed (P less than 0.001). It was concluded that initial immunocompetence, determined by parameters of cell-mediated immunity, shows strong prognostic association with the subsequently observed course of human breast cancer.
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PMID:Immunocompetence, immunosuppression, and human breast cancer. III. Prognostic significance of initial level of immunocompetence in early and advanced disease. 737 Sep 53

We followed the expression of several glutathione S-transferase subunits in altered foci, liver neoplasms and metastases produced in male Fischer 344 rats by a modified Solt-Farber protocol, to determine whether components of the resistant phenotype are lost during neoplastic progression. At 6 mo after initiation, altered foci and persistent nodules displayed increased immunohistochemical expression of glutathione S-transferase subunits Yf (pi-class), Ya (alpha-class) and Yb1 (mu-class) in comparison with normal or surrounding liver tissue. However, although most altered foci exhibited little change in glutathione S-transferase Yb2 (mu-class) subunit expression, 5% of Yf-positive foci and nodules were partially or completely deficient in Yb2 expression. At 12 and 18 mo after initiation, most grossly visible hepatocellular tumors retained induced expression of glutathione S-transferase subunits Yf, Ya and Yb1, but 63% of the carcinomas, 88% of the primary metastatic carcinomas and 94% of the pulmonary metastases were deficient in Yb2 expression. These differences in glutathione S-transferase subunit expression were confirmed by quantitative analysis by reverse-phase HPLC of S-hexylglutathione affinity-purified glutathione S-transferases from advanced tumors. Cytosolic glutathione S-transferase activity for trans-4-phenyl-3-buten-2-one in advanced tumors ranged from 42% to 66% of the activity in matched surrounding liver, whereas glutathione S-transferase activities for 1-chloro-2,4-dinitrobenzene were increased by 140% to 161%. These studies demonstrate that progression of hepatocellular carcinomas in the resistant hepatocyte model of carcinogenesis in which several glutathione S-transferase subunits are induced is associated with the loss of a major constitutive mu-class hepatic glutathione S-transferase. Although the mechanism and role of the reduction or loss of glutathione S-transferase Yb2 during malignant progression are unknown, we propose that loss of glutathione S-transferase Yb2 in some preneoplastic populations of hepatocytes might be conducive to further DNA damage by presently unknown environmental or endogenous compounds that are normally detoxified preferentially by glutathione S-transferase isoenzymes containing this subunit.
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PMID:Reduced expression of glutathione S-transferase Yb2 during progression of chemically induced hepatocellular carcinomas in Fischer 344 rats. 802 Aug 84


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