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)

In an attempt to understand some of the natural immunological characteristics of cutaneous melanoma so that we can plan justifiable immunotherapeutic approaches, 23 patients were studied. The autologous leukocyte migration inhibition assay was utilized to assess in vitro their tumor-specific cellular immunity. This assay was specifically used because when presensitized lymphocytes are exposed to the same antigen, they release lymphokines which inhibit the natural migration of the leukocytes. All the patients were staged pathologically according to the TNM system. Twelve of them had regional metastasis, i.e., stage III, and underwent regional lymphadenectomy. The other 11 had distant metastases, i.e., stage IV disease, and all their gross tumors were resected. These 23 patients were the source of tumor material and peripheral blood. Fresh autologous leukocytes were obtained for the assays, from each patient, on the day of surgery and prior to the administration of the preoperative medications. These were tested in vitro, on the same day, with freshly prepared autologous tumor extracts as the source of autologous tumor antigens. The results revealed that the preoperative leukocytes of patients with stage III melanoma expressed hypersensitivity to their tumors, with significant inhibition of their leukocyte migration, compared to those with distant metastases who expressed no such sensitivity, P = 0.012. Such hypersensitized lymphocytes may be capable of producing more efficient lymphokine activated killer (LAK) cells for an effective adjuvant adoptive immunotherapy.
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PMID:An immunological aspect of melanoma and its potential application in adjuvant therapy. 174 45

The impact of nodal tumor burden on patterns of relapse and survival was retrospectively analyzed in 1001 patients with stage III melanoma. The incidence of tumor recurrence within the node dissection field was lower in patients with 1 nodal metastasis (9%) or with no extranodal invasion (15%) than in patients with multiple involved nodes (15% to 33%) or connective tissue invasion (28%). Patients with 1 "positive" node (a node in which cancer was detected) had a 45% 5-year and 39% 10-year survival rate compared with patients who had 2 to 4 positive nodes (37% and 28%), 5 to 10 nodes (20% and 17%), more than 10 nodes (5% and 3%), or extranodal invasion (14% and 11%). The occurrence of in-transit metastases in 10% of patients after nodal dissection was not influenced by the extent of nodal tumor burden.
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PMID:Patterns of relapse in 1001 consecutive patients with melanoma nodal metastases. 277 7

The numbers of strongly adherent monocytes in the peripheral blood of normal subjects and cancer patients were determined. The method used was to place peripheral blood mononuclear cells in microwells and culture them for 1 week. At the end of that period, adherent macrophages were counted in the Coulter counter after release. Adherent cells per milliliter of blood, per total cells, and per mononuclear cells or monocytes plated were markedly diminished in the peripheral blood mononuclear cells of 44 melanoma, 23 breast cancer, 18 lung cancer, nine colon cancer, and 27 leukemia patients. Median values were 14.8 X 10(4) adherent cells per ml peripheral blood for 86 normal subjects, as against 2.5 X 10(4) per ml in the peripheral blood of the 125 patients (P less than 0.001). There was a poor correlation between the adherent cell numbers and the peripheral blood leukocyte counts, but an excellent correlation of the different adherent cell counts with each other. The number of adherent cells in the peripheral blood varied inversely with age in the cancer patients, but not in the normal subjects (r = 0.29, P less than 0.005). When patients under age 50 were compared to the controls, the deficiency of adherent cells was slightly more severe in patients with stage IV lung cancer than in those with stage III lung cancer. In contrast, there was no difference in the degree of deficiency between patients with stage III melanoma and no evident disease and patients with stage IV disseminated metastatic disease. The implications of these results are discussed.
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PMID:Deficient strongly adherent monocytes in the peripheral blood of cancer patients. 696 25

Immunohistochemical staining with monoclonal antibodies detected ICAM-1 in about 69% of 55 primary melanoma lesions and in about 89% of 28 metastatic lesions. The average number of melanoma cells stained by anti-ICAM-1 monoclonal antibodies was approximately 65% in both primary and metastatic lesions. ICAM-1 expression in primary lesions was significantly associated with their thickness. Furthermore, ICAM-1 expression in primary lesions was associated with a reduction in the disease-free interval and with survival. At variance with the information in the literature, the association with clinical parameters of the disease did not reach the level of statistical significance. This discrepancy is likely to reflect the inclusion in the present study of a small number of primary lesions with a thickness < 1.5 mm. At variance with recently published data, the level of serum ICAM-1 in 75 patients with malignant melanoma was found to be nonsignificantly different from that in 47 age- and sex-matched controls. The level of serum ICAM-1 was significantly increased only in patients with stage III melanoma with lesions and in those with stage IV melanoma. Two novel and clinically relevant findings of the present investigation are (a) the significantly higher serum ICAM-1 level in patients with liver metastases than in those with metastases in other anatomic sites and (b) the progressive increase of ICAM-1 level in serial blood samples from patients with disease progression. The latter findings suggest that monitoring of serum ICAM-1 level may represent a valuable noninvasive indicator system to detect liver metastases and to monitor the clinical course of the disease in patients with malignant melanoma.
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PMID:Clinical relevance of ICAM-1 expression in primary lesions and serum of patients with malignant melanoma. 810 88

DNA flow cytometry of the lymph node metastases from 56 patients was used to retrospectively evaluate the prognostic significance of DNA ploidy in patients with stage III melanoma. The findings were correlated with traditional prognostic factors and patient survival. Multivariate regression analysis revealed that, in addition to the number of positive lymph nodes and patient gender, the DNA index was a significant predictor of patient survival (all p < 0.03). Within this cohort of patients, the patients with the poorest prognoses were those with DNA indices greater than 2 (at least tetraploid), more than three positive lymph nodes, and male gender. There was a significant survival difference among the patients having zero, one, or two of these risk factors (p < 0.001). Our results indicate that DNA analysis of melanoma metastases by flow cytometry provides an additional discriminating factor for predicting patient outcome after therapeutic lymph node dissection. This information may be useful in directing patients with stage III melanoma at higher risk for recurrence into clinical trials of more aggressive systemic adjuvant therapy.
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PMID:Prognostic implications of DNA index in patients with stage III cutaneous melanoma. 827 43

We have developed a novel approach to cancer immunotherapy-an autologous whole-cell vaccine modified with the hapten dinitrophenyl (DNP). This approach elicits significant inflammatory responses in metastatic sites and some objective tumor responses. Post-surgical adjuvant immunotherapy with DNP-modified melanoma vaccine in a setting of micrometastatic disease produces significant survival prolongation in stage III melanoma patients. Histologically, the inflammatory responses of the tumor consist of infiltration by lymphocytes, the majority of which are CD8+, HLA-DR+ T cells. T cells from these lesions tend to have mRNA for interferon gamma. T cell receptor analysis suggests that the tumor-infiltrating T cells are clonally expanded. DNP-modified vaccine also induces T cells in the peripheral blood, which respond to DNP-modified autologous cells in a hapten-specific, MHC-restricted manner. Moreover, a T cell line generated from these lymphocytes responded to only a single HPLC fraction of MHC-associated, DNP-modified tumor peptides. Since inflammatory responses in metastases were not consistently associated with dramatic tumor regression, we considered the possibility of immunosuppression at the tumor site. We found that mRNA for the anti-inflammatory cytokine, interleukin-10 (IL-10) is expressed in most metastatic melanoma tissues and subsequently demonstrated that IL-10 protein is produced by melanoma cells. Thus the efficacy of DNP vaccine could be further enhanced by inhibition of IL-10 production or binding. Finally, we expect these results obtained with melanoma to be applicable to other human cancers.
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PMID:Active specific immunotherapy with hapten-modified autologous melanoma cell vaccine. 900 71

We have devised a novel approach to active immunotherapy based on modification of autologous cancer cells with the hapten, dinitrophenyl (DNP). The treatment program consists of multiple intradermal injections of DNP-modified autologous tumor cells mixed with BCG. Administration of DNP-vaccine to patients with metastatic melanoma induces a unique reaction- the development of inflammation in metastatic masses. Histologically, this consists of infiltration of T lymphocytes, most of which are CD8+. These T cells usually produce interferon-gamma in situ. Moreover, they represent expansion of T-cell clones with novel T-cell receptor (TCR) structures. Occasionally, administration of DNP-vaccine results in regression of measurable metastases. The most common site of regression has been small lung metastases. Administration of DNP-vaccine to patients in the postsurgical adjuvant setting produces a more striking clinical effect. Of 62 patients with clinically evident stage III melanoma who had undergone lymphadenectomy, the 5-year relapse-free survival rate was 45% and the overall survival rate was 58%. These results appear to be better than those obtained with high-dose interferon, although a randomized phase III trial is required to prove that point. A recent phase I study suggests that this therapeutic approach is also applicable to stage III ovarian cancer. There appear to be no insurmountable impediments to applying this approach to much larger numbers of patients or to developing it as a standard cancer treatment.
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PMID:Autologous, hapten-modified vaccine as a treatment for human cancers. 986 79

We have devised a novel approach to active immunotherapy based on modification of autologous cancer cells with the hapten, dinitrophenyl (DNP). The treatment program consists of multiple intradermal injections of DNP-modified autologous tumor cells mixed with BCG. Administration of DNP-vaccine to patients with metastatic melanoma induces a unique reaction - the development of inflammation in metastatic masses. Histologically, this consists of infiltration of T lymphocytes, most of which are CD8+. These T cells usually produce gamma interferon in situ. Moreover, they represent expansion of T cell clones with novel T cell receptor structures. Occasionally, administration of DNP-vaccine results in partial or complete regression of measurable metastases. The most common site of regression has been small lung metastases. Administration of DNP-vaccine to patients in the post-surgical adjuvant setting produces a more striking clinical effect. We have treated 214 patients with clinically evident stage III melanoma who had undergone lymphadenectomy. With a median follow-up time of 4.4 years (1.8-10.4 years) the 5-year overall survival (OS) rate is 47% (one nodal site = 51%, two nodal sites = 33%). These results appear to be comparable to those obtained with high dose interferon. More recent studies suggest that this therapeutic approach is also applicable to ovarian cancer. There appear to be no insurmountable impediments to applying this approach to much larger numbers of patients or to developing it as a standard cancer treatment.
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PMID:Autologous, hapten-modified vaccine as a treatment for human cancers. 1125 93

Elective lymph node dissection (ELND) is increasingly displaced by the Sentinel-lymph node biopsy. In this view we analyzed the efficacy of ELND in the treatment of malignant melanoma of the extremities and the trunc. Between 1979 and 1998 we performed a lymph node dissection in 834 patients (336 male, 498 female; average age 52 years). The analysis of the prospectively collected data was based on those 650 patients in whom an ELND was performed for UICC-stage I (T2) to stage III melanoma. The 5-year survival rate was 75% for all 650 patients. It was 87% for patients suffering from stage I-disease (T2-n = 65), 86% for those with stage II-disease (n = 354) and 47% in case of stage III-disease (n = 231) respectively. In 7 of the 73 patients undergoing ELND for a T2-tumor, in 56 of the 424 patients suffering from T3-tumor and in 38 of the 153 patients with a T4-tumor clinically obvious lymph node metastases had been detected by ELND. Discerning our results, we could demonstrate that a few of our patients profited from ELND, namely the patients in those clinically obvious metastases could be detected and survival could be achieved, i.e. 29 of all 650 electively dissected patients (2 of 7 T2N1-patients, 18 of 56 T3N1-patients and 9 of 38 T4N1-patients). We regard this benefit as an argument not to abandon the histological evaluation of the regional lymph nodes. However, because of the limited efficacy of elective lymphadenectomy, ELND should be displaced by the less invasive Sentinel-lymph node biopsy.
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PMID:[Efficacy of elective lymph node dissection in malignant melanoma of the extremities and trunk. An analysis in view of the sentinel lymph node biopsy]. 1137 Mar 89

The use of tyrosinase-based polymerase chain reaction (PCR) tests for the detection of circulating tumour cells in the blood of melanoma patients has led to highly controversial results. We here report on the analysis of 120 blood samples from 76 stage I to IV melanoma patients using a new MART-1/Melan-A PCR system in conjunction with the tyrosinase-specific assay reported in the literature. While there were no positive results in localized disease (stages I and II), identification of specific PCR products in stage III melanoma patients was restricted to the MART-1/Melan-A tests, with positive results in 11% (two out of 19) of the blood specimens analysed. Stage IV melanoma patients presented with the highest incidence of detectable mRNA levels, with positive results for tyrosinase in 38% (12 out of 32) and for MART-1/Melan-A in 22% (seven out of 32). By delineating 64 follow-up specimens covering sampling periods of up to 33 weeks, stable mRNA expression profiles were identified in nearly 95%. Four patients, however, showed PCR changes towards positive MART-1/Melan-A expression that were linked to metastatic melanoma progression. Taken together, PCR tests for tyrosinase and MART-1/Melan-A seem to lack sufficient detection frequencies for the routine monitoring of melanoma disease. Regarding the link between MART-1/Melan-A seroconversion and the development of metastatic disease, further studies are needed to clarify the clinical value of this observation.
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PMID:MART-1/Melan-A and tyrosinase transcripts in peripheral blood of melanoma patients: PCR analyses and follow-up testing in relation to clinical stage and disease progression. 1159 94


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