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

One hundred and fifty-six patients were screened for the presence of urinary melanoma antigen and serum cytoplasmic antibody. It was found that 44% of symptomless Stage 1 patients tested five to 15 years after operation had detectable antigen (Ag) in their urine; the urines of 67% of Stage 2A (local recurrence) patients were positive for Ag; while in only 38% of those patients graded 2B (lymph-node involvement) were these tests positive. Urines of 83% of patients with generalized metastases (Stage 3) were positive. A sequential study was made of 23 patients seen and treated in 1976. Of this group, 14 reverted from a positive state to a negative one following excision of their tumour, while six were negative on first postoperative testing and subsequently became positive. Three out of the 23 remained persistently negative. T lymphocyte levels were assessed in 71 melanoma patients, and a stage-related fall was noticed. Thymosin (Hoffman LaRoche) on in vitro incubation significantly raised the levels of T lymphocytes.
 ...
PMID:The significance of urinary melanoma antigen excretion and the ability of thymosin to raise the level of depleted lymphocytes in vitro in malignant melanoma. 30 81

To determine whether the pulmonary metastases of melanoma cells could be inhibited, C57BL/6 mice were immunized with an anti-idiotypic antibody, 7C4, corresponding to a mouse melanoma antigen. Three groups of mice were compared: 1) 7C4-immunized group which received an injection of 100 micrograms of 7C4 in Freund's complete adjuvant (FCA) subcutaneously on day -21 followed by intraperitoneal injections of the same dose on days -14 and -7,2) adjuvant-treated control group administered with only FCA, and 3) untreated control group. On day 0, 5 x 10(5) of BL6 cells were injected into the caudal vein of all mice. Two weeks later, they were sacrificed and their lungs were removed. The number pulmonary metastatic colonies present on the lung surface were counted and compared among the groups. The length of survival days was also compared. The 7C4-immunized group showed an average of 166 +/- 44 colonies as compared to more than that of 300 colonies in each control groups, and a significant difference was observed (P < 0.01). The immunized group survived significantly longer than the control group (Greenwood's formulation) on day 23 (P < 0.01). Thus the immunization with 7C4 effectively inhibited lung metastasis of melanoma cells. These findings suggest that vaccination with anti-idiotypic antibody to tumor antigen is effective on inhibiting tumor metastasis.
 ...
PMID:Effect of immunization with anti-idiotypic antibody to melanoma antigen on lung metastasis in mice. 130 79

Melanoma antigen vaccines are a conceptually attractive approach to prevent or delay disease recurrence in patients with surgically resected malignant melanoma. However, the immunogenicity of current vaccines is relatively low. Cyclophosphamide, when given in low doses prior to antigen exposure, is an immunomodulator which has been shown to enhance both humoral and cellular antitumor responses in animals and humans. We conducted a prospective, randomized, clinical trial to study whether pretreatment with cyclophosphamide augments the immunogenicity of a polyvalent, allogeneic, melanoma antigen vaccine in patients with melanoma and low tumor burden. Forty-five patients with resected stage II melanoma (regional metastases) were randomly allocated to treatment with melanoma vaccine or melanoma vaccine plus cyclophosphamide. All patients received the same dose and schedule of vaccine immunizations; those randomized to cyclophosphamide received 300 mg/m2 i.v. 3 days prior to each vaccine immunization. Cellular immune responses were evaluated by delayed-type hypersensitivity (DTH) skin reactivity to a test dose of vaccine at baseline (prior to treatment) and following the fourth immunization. Humoral immune responses were measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiographic analysis of indirect immunoprecipitates of patients' sera at the same time points. Twenty-four patients were randomized to cyclophosphamide pretreatment and 21 to vaccine alone; 22 and 18 patients were evaluable in each group, respectively. Differences were statistically nonsignificant with respect to either cellular (DTH) or humoral (antibody) responses between the two groups. DTH responses were induced in 16 of 22 (73%) and 15 of 18 (83%) patients treated with cyclophosphamide plus vaccine and vaccine alone, respectively. The mean posttreatment augmentation in DTH response in the cyclophosphamide group was 9.5 mm, compared with 9.9 mm in the vaccine-only group. Eight of 12 (66%) cyclophosphamide-pretreated patients and 9 of 12 (75%) vaccine-only patients produced increased titers of antimelanoma antibodies following treatment. No differences were observed between the groups in disease-free or overall survival. In summary, low-dose cyclophosphamide pretreatment failed to augment the immunogenicity of a polyvalent, allogeneic, melanoma vaccine in patients with completely resected early-stage melanoma.
 ...
PMID:Lack of effect of cyclophosphamide on the immunogenicity of a melanoma antigen vaccine. 206 22

Using B16 F10 murine melanoma cells and sublines generated from the JB/MS melanoma which exhibit various degrees of melanogenesis, the relationships among differentiation, tumorigenicity, and metastatic potential were examined. The effect of melanocyte-stimulating hormone (MSH), which specifically stimulates differentiation of melanocytes, was also studied. All melanoma lines tested were capable of growing as experimental pulmonary metastases but, surprisingly, the undifferentiated and amelanotic JB/MS-w cells failed to grow as primary subcutaneous tumors. JB/MS-w cells, which had few surface MSH receptors, did not respond to MSH with an increase in melanin production, unlike the other cell lines. Although in vitro treatment with MSH did not change the rates of growth of primary tumors by these cell lines, such treatment decreased the number of pulmonary metastases from B16 F10, JB/MS cells, JB/MS-b1 cells and JB/MS-w cells. Conversely, MSH treatment significantly increased the rates of pulmonary metastases from JB/MS-p cells. The expression of surface melanoma antigens, urokinase-type plasminogen activity and susceptibility to natural killer cells were examined. MSH did not significantly alter surface melanoma antigen expression, but increased the natural killer cell susceptibility of B16 F10, JB/MS and JB/MS-b1 cells, cells which possess abundant surface MSH receptors. There was an inverse correlation between differentiation (pigmentation) and proliferation in vitro, and the more pigmented melanoma cells (B16 F10, JB/MS and JB/MS-b1) expressed relatively lower levels of class-I MHC, relatively higher levels of class-II MHC and the highest metastatic capacity. These results demonstrate that MSH possesses the capacity to regulate not only melanogenesis, but also other factors critical to the metastatic growth of the cells.
 ...
PMID:Differentiation and the tumorigenic and metastatic phenotype of murine melanoma cells. 216 2

69 patients with different tumors (colorectal, melanoma, testicle, ovary, bladder, carcinoid, lungs) were investigated by radioimmunoscintigraphy. The corresponding antibodies or their F(ab')2 fragments against CEA (n = 30), melanoma antigen (n = 25), TPA (n = 6), beta-HCG (n = 5), HMFG-2 (n = 2) and CEA/CA 19-9 (n = 1) were selected on the basis of immunohistochemical investigations of the primary tumors. The precision was 62%, and the number of false-negative findings was 32%. Additional clinical information (detection or exclusion of a suspected recurrence) could be obtained in 22 patients. From these results, it can be concluded that the corresponding tumor antibodies should be selected on the basis of immunohistochemical investigations of the primary tumor before performing radioimmunoscintigraphy to screen for recurrences or metastases.
 ...
PMID:[Scintigraphic detection of malignancies with radioactively labelled tumor antibodies. Clinical results based on immunohistochemical research]. 243 96

A monoclonal antibody raised against the high molecular weight melanoma antigen was labelled with indium-111 and injected intravenously into 25 patients with malignant melanoma. The results obtained from images at 24 and 96 h post i.v. administration of the antibody were compared with results obtained from computerised tomography studies with regard to detection of previously unrecognised sites of metastatic disease and apparent false positive localisation. Detailed study of the patients' clinical condition and detection rates using the two methods suggest that both methods detect approximately 80% of clinically and pathologically confirmed metastases. Of 62 known metastases, the antibody detected 50 (81%), with 17 false positive results. False negatives were most common in the lung. In eight patients the two methods were considered of equal value, in 10 the monoclonal gave a greater amount of clinically relevant information, and in seven the CT was superior. In three patients clinically significant metastatic lesions were detected by the radiolabelled monoclonal and had not been previously recognised either by CT scanning or on clinical grounds. No patients had any adverse reaction to the antibody and in the course of our study the dose of antibody was reduced from 20 mg to 200 micrograms with no apparent loss of sensitivity. In at least two patients uptake of the labelled monoclonal into tumour sites would have been adequate for effective targeted radiotherapy.
 ...
PMID:A comparative study of the relative sensitivity and specificity of radiolabelled monoclonal antibody and computerised tomography in the detection of sites of disease in human malignant melanoma. 271 45

Radioimmunoscintigraphy was performed in 52 patients with a variety of malignant tumors (colorectal, melanoma, lung, testicular, ovarian, bladder, carcinoid). Respective antibodies or their F(ab')2 fragments against CEA (n = 23), melanoma antigen 225.28 S (n = 18), TPA (n = 4), beta HCG (n = 5) and HMFG2 (n = 2) were selected by immunohistochemistry of the primary tumor. Most patients were suspected of recurrence or of hitherto unknown distant or local metastases. Overall accuracy was 61% (32/52). False negatives amounted to 33% (17/52). Useful additional clinical information-not available by CT, ultrasonics or serum levels of tumor markers-was obtained in 17 out of 52 patients (= 33%). From these results it seems obvious that antibodies used for radioimmunoscintigraphy should be selected on the basis of immunohistochemistry.
 ...
PMID:Clinical results of immunoscintigraphy in a variety of malignant tumors with special reference to immunohistochemistry. 354 Aug 57

A polyvalent melanoma tumor antigen vaccine was prepared from antigens shed by a pool of human melanoma cells cultured in serum-free medium. The vaccine contained multiple melanoma associated antigens (MAAs) and was free of detectable fetal calf serum (FCS) proteins and Dr antigens. Three batches of vaccine prepared several months apart contained the same spectrum of tumor antigens. Thirteen patients with metastatic malignant melanomas were immunized intradermally with escalating doses of the vaccine in a Phase I study. There was no toxicity other than transient urticaria at the injection site. Humoral immunity, assayed by indirect immunoprecipitation, was augmented in five (38%) patients. Cellular immunity, assayed by delayed-type cutaneous hypersensitivity, was induced in four (31%) patients. Skin tests to a control vaccine prepared from pooled allogeneic lymphocytes were negative. Cutaneous metastases regressed completely in one patient who is now disease free after 2 years, and multiple cutaneous metastases have remained stable for 14 months in another patient. These results indicate that active immunization to a partially characterized polyvalent melanoma antigen vaccine is safe and can increase immunity to melanoma in some patients.
 ...
PMID:Preparation and characterization of a polyvalent human melanoma antigen vaccine. 372 38

Four methods were compared for identifying amelanotic and oligomelanotic melanomas in paraffin sections of formalin-fixed metastases from subjects with primary cutaneous melanomas. Of the amelanotic and oligomelanotic metastases a characteristic pattern of fluorescence was seen with an incident-light fluorescence microscope in 11 of 25 (44%); the Warthin-Starry stain at pH 3.2 was positive in 14 of 25 (56%); these two procedures together were a little more effective, 63% positive; S100 protein was revealed by immunoperoxidase staining in 26 of 28 (93%); the monoclonal antibody NKI/C-3 against a human melanoma antigen gave positive immunoperoxidase staining in 24 of 27 cases (89%). Of the pigmented metastases S100 protein was demonstrated in 18 of 21 (86%) and NKI/C-3 gave positive staining in all 20 tested. These antibodies are not specific for melanoma but a metastasis which does not react with either antibody is unlikely to be melanoma.
 ...
PMID:A comparison of some methods for identifying amelanotic and oligomelanotic melanoma metastases in paraffin sections. 390 Aug 99

Three established lines of melanoma cells were derived from anatomically distinct metastases occurring in a single patient (DX). The lines, DX-1, DX-2, and DX-3, showed marked phenotypic diversity, as indicated by characteristic differences in growth rate, morphology, pigmentation, and the expression of surface antigens and glycoproteins. DX-1 and DX-3 expressed HLA-DR products, whereas DX-2 lacked HLA-DR expression. DX-1, DX-2, and DX-3 could also be distinguished on the basis of the profile of radiolabeled glycoproteins. Additional quantitative differences in the surface antigenic phenotype of the three cell lines were revealed by serological tests with a battery of monoclonal and conventional antibodies defining melanoma differentiation antigens. In tests for autologous humoral immunity to melanoma cells, sera from patient DX were found to have IgG antibody that reacted with surface antigens of DX-2 cells; no autologous reactivity was seen with DX-1 or DX-3 target cells or with three more recently established melanoma cell lines from patient DX. Absorption analysis indicated that the antigen detected by DX sera on DX-2 cells is a class 1 melanoma antigen, having been detected only on DX-2 cells and in much lower but demonstrable amounts on DX-1 and DX-3 cells. No other cell type, including DX normal fibroblasts, DX B cells, or 45 allogeneic melanoma cell lines expressed the class 1 antigen of DX melanoma. The fact that only one of the melanoma cell lines derived from patient DX was suitable target for the detection of autologous class 1 reactivity has implications for the study of human tumor antigens and may explain why antibody to class 1 antigens has been found so infrequently in past studies of melanoma patients.
 ...
PMID:Heterogeneity in surface antigen and glycoprotein expression of cell lines derived from different melanoma metastases of the same patient. Implications for the study of tumor antigens. 697 7


1 2 3 4 Next >>