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)

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.
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PMID:Lack of effect of cyclophosphamide on the immunogenicity of a melanoma antigen vaccine. 206 22

Melanoma involving the ciliary body is a rare tumor which carries a poor prognosis when compared to all uveal melanoma. We have treated 54 patients with ciliary body melanoma using helium ions from 1978 to 1985. Because of the high rate of metastatic disease, the 5-year disease specific survival rate is only 59% despite a 5-year local control rate of 98%. The greatest diameter of the tumor was predictive of loss of vision and enucleation (p = .05, p = .04, respectively). Multivariate analysis showed that the greatest diameter of the tumor was the most important predictor of death from metastases. The incidence of neovascular glaucoma at 5 years is 43%. The 5-year actuarial rate of enucleation is 26%. Enucleation was done for pain and/or neovascular glaucoma. Univariate analysis showed treatment volume to be a statistically significant predictor for the development of neovascular glaucoma (p = .0017) and enucleation (p = .0078). Seventy percent of neovascular glaucoma occurred in patients with treatment volume greater than 5.5 cc. Seventy-four percent occurred in patients with an initial ultrasound height greater than 9.2 mm. Using this information, patients at high risk for neovascular glaucoma could be considered for prophylactic treatment with panretinal photocoagulation.
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PMID:Ciliary body melanoma treated with helium particle irradiation. 211 91

Melanoma vaccines are an exciting and increasingly attractive immunotherapeutic approach for malignant melanoma. Vaccines can be used for patients with high risk primary melanoma and regional disease, stages in the progression of melanoma for which there is presently no treatment. They are unique in their potential to prevent cancer in high risk individuals. Multiple approaches are being followed to develop effective vaccines. It is too early to judge whether any of them effectively slow the progression of melanoma. However, it is clear that vaccines are safe to use, and that they can stimulate immune responses to melanoma in some patients. The specificity of these responses needs to be clarified, and multiple challenges remain to be overcome before effective vaccines to melanoma become available. We must first identify the antigens on melanoma that stimulate immune responses, define the immune effector mechanisms that are stimulated by vaccine immunization and identify those responsible for increasing resistance to tumor growth, devise appropriate ways of constructing vaccines that will induce such responses, and find adjuvants and/or immunodulators that will potentiate desirable immune responses.
Cancer Metastasis Rev 1990 Jul
PMID:Tumor vaccines. 220 70

The successful use of iodine-131-meta-iodobenzylguanidine (I-131-MIBG) scintigraphy for diagnosis of phaeochromocytoma and neuroblastoma stimulated investigation into its diagnostic and therapeutic usefulness in other neural crest tumours. It appears that there is a difference in capacity to absorb I-131-MIBG between the different tumour types. In I-131-MIBG scintigraphy of carcinoids there are more false negative results in comparison with phaeochromocytomas and neuroblastomas. Melanoma, also a neural crest tumor, turned out to be false negative in 100% of the cases reported until 1989. The authors present a case of a malignant melanoma with metastases in liver and stomach, concentrating I-131-MIBG. Biochemical examination demonstrated that this particular tumour was metabolically very active. It is suggested that the I-131-MIBG-positive scintigram of the melanoma may be related to the level of metabolic activity. By biochemical screening in proven cases of malignant melanoma it may be possible to select cases in which I-131-MIBG scintigraphy is worthwhile with a view to therapeutic application of I-131-MIBG.
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PMID:[Scintigraphy using I 131 iodobenzylguanidine and malignant melanomas]. 223 80

Fifty-six patients with symptomatic metastatic melanoma of the gastrointestinal tract (GIT) treated surgically at the Sydney Melanoma Unit between 1974 and 1989 were reviewed. The majority of these patients presented with abdominal pain or symptoms of anemia. The small intestine was the site of metastasis in more than 80 per cent. The mean over-all survival time was 11.7 months (range of one to 60 months) after surgical treatment of a first metastasis to the GIT and 3.6 months (range of zero to 12 months) postoperatively for a second GIT metastasis. Forty-four of the patients reported complete relief of their symptoms postoperatively. The results suggest that an aggressive approach to symptomatic GIT metastases from malignant melanoma is justified both to relieve distressing symptoms and to prolong life.
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PMID:The justification for surgical treatment of metastatic melanoma of the gastrointestinal tract. 223 26

A retrospective search of patients seen at the Duke Melanoma Clinic from 1970 to 1986 identified 308 clinically Stage I patients, with 4.0 to 10.0 mm cutaneous melanomas. Five-year and ten-year survival was 56% and 43%, respectively. Elective lymph node dissection (ELND) was done in 116 patients (37.7%); there was no difference in disease-free interval (DFI) or survival between these patients versus patients treated with wide excision only (P = 0.9). Thirty-two patients (27.6%) had pathologically positive nodes on ELND. These patients had a shorter DFI (P = 0.05) and survival (P = 0.03) compared with patients with negative node dissections. When further divided by Breslow's thickness, this difference persisted in patients with 4.0 to 6.0 mm lesions (P = 0.01). However, for thicker lesions (greater than 6.0 mm), there was no difference in survival between the node-negative and node-positive groups (P = 0.9). The mean follow-up was 7.1 years. Elective lymph node dissection was not done in 192 patients; 78 of these recurred first in the regional nodes. These 78 patients were compared with the 32 patients who had pathologically positive nodes by ELND to see if patient survival was improved by early removal of nodal disease. There was no difference in DFI (P = 0.5) or survival (P = 0.3) between these two groups. It is concluded that ELND may provide prognostic information for patients with thick cutaneous melanomas. However, there was no change in DFI or ultimate survival when patients were followed, and nodes removed when clinically positive. The authors do not recommend ELND for patients with thick melanomas because the risk of distant metastases outweighs any benefit of regional node dissection.
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PMID:The role of elective lymph node dissection in the management of patients with thick cutaneous melanoma. 224 94

A retrospective analysis of malignant melanoma of the upper aerodigestive tract treated in Scotland between 1976 and 1988 has been performed to define the incidence, clinical features and response to treatment. Using the Scottish Melanoma Group database and pathology and oncology department registers 32 patients, 20 female, 12 male, were identified, representing a population incidence of approximately 0.5 per million per year. The median age was 69 years, range 38-86. Tumour arose in the nose or sinuses in 23 cases and the oral cavity or pharynx in eight cases. Metastases were present at presentation in four cases. Radical treatment was attempted in 27 patients: radiotherapy alone in 13, surgery alone in 10 and combined modality treatment in four. Complete regression, which was sustained in five cases, occurred in eight of the 13 radically irradiated patients; whereas sustained local control was achieved by radical surgery in only four of ten patients. The median survival is 14 months, non lived more than 63 months. Only one patient is alive and disease free, three more survive with disease. Of the 28 who had died, nine had local tumour only, nine metastases only and ten both local and distant disease. Outcome was not affected by age, sex, primary site or nodal spread.
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PMID:Mucosal melanomas of the head and neck: The Scottish experience. The Scottish Melanoma Group. 226 28

Melanoma is often diagnosed in young adults, a significant proportion of whom are women of child-bearing age. The prognosis of women diagnosed with melanoma during a pregnancy continues to be debated. One hundred patients, ages 19 to 40 years, have been identified who were pregnant at the time of diagnosis of their melanoma. All were treated with local excision. Sixteen per cent underwent elective lymph node dissections. Immunotherapy was administered to 83% of patients. Mean follow-up was 6.8 years from the date of diagnosis. The patients were compared to an age-matched group of 86 women who were not pregnant at the time of diagnosis. Overall mortality during the follow-up period was 25% in the pregnant group and 23% in the control group. Among the pregnant group, there was an increased incidence of lymph node metastases during the follow-up period (39% versus 26%, p = 0.053). Among stage I patients, there was a significantly shorter DFI for the pregnant group (p = 0.039), with 50% of pregnant patients and 67% of control patients free of disease at 10 years. Similarly, among stage 1 patients, the time to development of lymph node metastases was shorter in the pregnant group (p = 0.021). Multivariate analysis demonstrated that pregnancy at diagnosis was significantly associated with the development of metastatic disease (p = 0.008), when controlling for tumor site, thickness, and Clark level. Patients who developed melanoma during pregnancy did not, however, have a significant decrease in survival.
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PMID:Malignant melanoma arising during pregnancy. A study of 100 patients. 233 17

Melanoma is increasing in incidence. An often-unsuspected complication is metastasis to the gastrointestinal tract, which leads to bowel obstruction or intussusception. The most common symptoms in patients with gastrointestinal metastasis are vomiting, abdominal pain and abdominal distention. Metastatic disease should be suspected in any patient with gastrointestinal symptoms and a history of cutaneous melanoma.
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PMID:Melanoma metastatic to the gastrointestinal tract. 240 21

We used flow cytometry to measure the expression of human melanoma antigens on cell suspensions dissociated from metastatic masses. The objective was to study the heterogeneity between tumor samples from different patients and between different tumors excised from a single patient. Fifty-three metastases excised from 34 melanoma patients were analyzed with a panel of nine murine monoclonal antibodies (MOABs). Melanoma cells were stained by an indirect fluorescent method and analyzed on a Coulter EPICS C flow cytometer after gating to exclude tumor-infiltrating leukocytes and dead cells. The most consistently and most strongly expressed antigen was the high-molecular-weight proteoglycan (detected by the MOAB 9.2.27), which was expressed on 95% of the melanoma specimens and by a high proportion of cells within each specimen (mean +/- SE, 79.2 +/- 5.5). However, strong expression of this antigen was limited to melanoma cells that had been dissociated mechanically and was markedly diminished by exposure to collagenase. Culture of collagenase-dissociated tumor cells for 24 to 48 h resulted in reexpression of the antigen. The expression of other melanoma-associated antigens was not affected by collagenase treatment, but for these antigens there was more variability between cells from an individual tumor and between tumors from different patients. The percentage of enzyme-dissociated tumors considered positive for MOAB binding (defined as at least 10% of cells positive) and the mean +/- SE of the percentage of positive cells within a tumor were as follows: MOAB ME-9-61 (antigen, p97) = 84% + (41.2 +/- 5.4%); MOAB ME-20.4 (antigen, nerve growth factor receptor) = 40% + (18.7 +/- 5.1%); MOAB ME-24 (antigen, ganglioside GD3) = 84% + (50.8 +/- 4.8%); MOAB ME-311 (antigen, ganglioside 9-O-acetyl-GD3) = 76% + (42.5 +/- 5.1%); MOAB ME-361 (antigen, mainly ganglioside GD2) = 3% + (1.9 +/- 0.8%); MOAB 3F8 (antigen, ganglioside GD2) = 36% (10.5 +/- 3.8%); MOAB 14G2a (antigen, ganglioside GD2) = 86% + (46.0 +/- 6.7%); MOAB L243 (antigen, HLA-DR) = 56% + (22.5 +/- 5.5%). In 19 cases, we were able to compare the antigenic profiles of two tumors excised from the same patient at different times. Analysis by nonindependent t test showed no significant differences in MOAB binding between the paired tumors. Moreover, linear regression analysis indicated that there was a linear relationship, with a slope approximately = 1, between the percentage of positive cells in Tumor 1 versus Tumor 2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Flow cytometric determination of the frequency and heterogeneity of expression of human melanoma-associated antigens. 258 30


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