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 effect of systemic BCG therapy on advanced melanoma was studied in 42 patients with stage II and stage III disease. Evaluation of the immune response prior and during therapy revealed that patients who failed to convert a negative purified protein derivative (PPD) reaction and those having a low stimulation ratio of lymphocyte cultures had rapidly progressive disease and short survival. Neither tumor regression nor prolongation of survival could be appreciated in patients with stage III disease. Furthermore, aggravation of symptoms was observed in patients with visceral metastases. Fifty percent of the patients with stage II melanoma treated by operation and adjuvant immunotherapy had recurrent or metastatis disease within two years. No adverse effects were noted in patients with early disease who received adjuvant therapy. Two patients who had a full course of systemic BCG therapy developed severe reactions after intralesional injection of the vaccine. Further experience with various immunotherapeutic regimens and longer follow-up are necessary to evaluate its value in the early stages of melanoma.
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PMID:Effectiveness of systemic BCG therapy in advanced melanoma. 84 15

The present study was performed to determine if postoperative systemic BCG adjuvant immunotherapy would improve survival in patients with pathologic stage II melanoma of the head and neck. Seventeen of twenty-five (68 per cent) patients treated with BCG are free of disease, whereas only seven of seventeen (40 per cent) patients treated by radical neck dissection alone are free of disease. Clark's technic for determining the level of invasion of the primary lesion was used to predict the presence of metastatic tumor in regional lymph nodes. Results indicate that patients with pathologically confirmed lymph node metastases from melanoma of the head and neck benefit from postoperative BCG adjuvant immunotherapy.
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PMID:Results of BCG adjuvant immunotherapy for melanoma of the head and neck. 101 38

This first metanalysis of melanoma from treatment centers worldwide consisted of 15,798 patients with localized melanoma (stages I and II) and 2,116 stage II melanoma patients with nodal metastases. Comparisons of dominant prognostic variables showed consistent results from center to center, despite the heterogeneity of the patient population. Six of eight centers that performed a multivariate analysis ranked ulceration among the first three most dominant prognostic factors. Men had a higher proportion of ulcerated lesions than did women. There was a positive correlation between ulceration and thickness. Patients with melanoma of the scalp had a worse prognosis than did those with lesions of the face and neck; those with melanomas on the hands had a significantly worse prognosis than did those with lesions on the arms or legs. In this study, women had a statistically significant survival advantage over men. Their melanomas arose in more favorable sites, were thinner, and less ulcerative and had a lower stage of disease at presentation. Stage III melanomas were more common in males, thicker, and more ulcerated and had a nodular growth pattern. Patients with clinically occult nodal metastases detected by pathological examination and those with a single metastatic node fared the best. Five of six centers identified the number of metastatic nodes to be the most significant prognostic factor. Distant metastases (stage IV were analysed at only two centers, which found that the number and site of metastases appeared to be the dominant prognostic features of stage IV melanoma. When all factors were analyzed in a Cox regression analysis, the dominant factors for stage IV melanoma patients were (1) the number of metastatic sites, and (2) the remission duration. There were no histologic criteria of the primary melanomas that predicted the patient's clinical course once distant metastases had developed.
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PMID:Cutaneous melanoma: prognosis and treatment results worldwide. 143 50

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

The prognostic role of cell kinetics (expressed as 3H-thymidine labelling index, 3H-TdR LI) was assessed on 145 patients with pathologic stage II melanoma subjected only to therapeutic lymph node dissection. The 3H-TdR LI determined on metastatic nodes was related to relapse-free survival and to survival. In particular, 3-year relapse-free survival was significantly different from patients with slowly and rapidly proliferating melanomas (40% vs 22%, P = 0.007), and this finding was consistently found for overall survival (68% vs 46%, P = 0.007). Moreover, in patients with high 3H-TdR LI tumours, the risk of relapse and death within the first year from lymphadenectomy was two-fold that of patients with low 3H-TdR LI tumours. Multiple regression analysis showed that 3H-TdR LI retained its prognostic significance on relapse-free and on overall survival even when the number of involved nodes and type of nodal metastases were considered. Present findings suggest that 3H-TdR LI can contribute to select high-risk stage II melanoma patients.
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PMID:Cell kinetics: an independent prognostic variable in stage II melanoma of the skin. 224 75

To determine the prognosis of patients with lymph node metastases from an unknown primary melanoma, we retrospectively reviewed the clinicopathologic features of 188 such patients treated from 1971 through 1986 and compared their records with those of patients with clinical stage II melanoma with known primary lesions. Patients with lymph node metastases from an unknown primary melanoma represented 4.6% of all patients with melanoma treated during that period. The five- and ten-year survival rates were 42% and 40%, respectively (median, 37 months). When stratified by number of tumor-containing lymph nodes, there was no significant difference in survival between patients with an unknown primary melanoma and lymph node metastases and those with clinical stage II melanoma and known primary sites. The prognosis of the former patients is no worse than that of patients with lymph node metastases from a known primary site and should be treated in a comparable manner.
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PMID:Surgical treatment of lymph nodes with metastatic melanoma from unknown primary site. 368 12

We determined the concentration of L-dopa in the plasma of 98 patients with biopsy-proven melanoma, a dermatological neoplasm that is characterized biochemically by abnormal tyrosine metabolism. For 21 patients previously diagnosed as having melanoma but who were clinically free of disease (stage I), the mean concentration of L-dopa in plasma, 1.01 (SD 0.12) micrograms/L, was not significantly different from that of 32 normal controls, 1.23 (SD 0.16) micrograms/L. However, L-dopa was increased significantly (p less than 0.001) in the plasma of all of 65 patients with active disease (stage II), 2.08 (SD 0.46) micrograms/L, and was highest in 12 patients with stage III malignant melanoma, 8.40 (SD 3.50) micrograms/L. The development of metastases in four patients with stage II melanoma was accompanied by an increase in the concentration of plasma L-dopa. These studies suggest that measurement of plasma L-dopa may be useful in the diagnosis of melanoma.
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PMID:Plasma L-dopa in the diagnosis of malignant melanoma. 394 Jun 99

Our aim was to identify and delineate alterations in the distribution and immunophenotype of the lymphocytes and paracortical dendritic leucocytes (interdigitating dendritic cells; IDCs) in lymph nodes regional to tumours. Using immunocytochemistry and computer-assisted image analysis we examined 65 lymph nodes excised from 47 patients with malignant melanoma. Twenty-nine patients had American Joint Committee on Cancer (AJCC) stage II melanoma (no tumour spread beyond the primary site) and 18 had AJCC stage III disease (metastases in the regional nodes). There were significant differences in the frequency, morphology, immunophenotype and anatomical distribution of the IDCs and in the complexity of their dendritic processes in different areas within individual lymph nodes. We conclude that morphological and phenotypical variations in IDCs correlate with differing levels of antigen presentation. Downregulation of antigen presentation in lymph nodes regional to tumours is most probably mediated by tumour products. Differences in IDC distribution and characteristics in lymph nodes from different anatomical sites must be considered in interpreting studies of nodal morphology and function.
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PMID:The morphology, immunophenotype and distribution of paracortical dendritic leucocytes in lymph nodes regional to cutaneous melanoma. 1147 29

In this study, the prevalence of additional positive lymph nodes in subsequent complete lymphadenectomy specimens for patients with early-stage melanoma of the head and neck, after positive sentinel lymphadenectomy results, was retrospectively analyzed. In the past 5 years at the authors' institution, 23 consecutive patients with clinical stage I or stage II melanoma of the head and neck underwent complete lymphadenectomies after positive sentinel lymph node biopsies and wide local excisions of the primary lesions. Sentinel lymph nodes were identified with intraoperative lymphatic mapping techniques (radiolymphoscintigraphy and vital blue dye injection) and were examined with routine histological methods and immunohistochemical staining for S-100. All lymph nodes harvested in complete lymphadenectomies were examined with routine histological techniques. Twenty-one patients (91.3 percent) demonstrated no additional positive lymph nodes in subsequent complete lymphadenectomy specimens; two patients (8.7 percent) each demonstrated one additional positive lymph node in the complete lymphadenectomy specimens. Both patients had ulcerated primary lesions more than 5 mm in depth. No patient developed a regional nodal recurrence during a mean follow-up period of 23.7 months (range, 2 to 56 months). The low prevalence of additional positive lymph nodes in complete lymphadenectomy specimens suggests that when microscopic metastases exist in the regional nodal basin, most of the time they are confined to the sentinel lymph nodes of patients with early-stage melanoma of the head and neck. Nevertheless, the question of whether subsequent complete lymphadenectomy is still necessary for this subgroup of patients warrants further study.
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PMID:Prevalence of additional positive lymph nodes in complete lymphadenectomy specimens after positive sentinel lymphadenectomy findings for early-stage melanoma of the head and neck. 1545 70

Cyclooxygenase 2 (COX-2) is an inducible enzyme involved in the production of prostaglandins and thromboxanes during inflammation. There are now several lines of evidence indicating that increased expression of COX-2 plays a functional role in the development and progression of malignant epithelial cancers. However, there is only limited data regarding the role of COX-2 in melanoma pathogenesis. In the present work, we retrospectively examined lesions through out the development of melanoma and metastatic disease (dysplastic nevi n = 10, melanoma in situ n = 4, stage II melanoma n = 10, stage III n = 4, stage IV n = 3, stage V n = 2, melanoma metastasis lymph nodes n = 13 metastasis to other sites n = 3). COX-2 was consistently observed in keratinocytes, dermal fibroblasts, and inflammatory cells in regions adjacent to benign evi and primary cutaneous melanomas. However, no COX-2 staining was detected in the nevi nor in the primary skin melanoma cells. In addition, COX-2 was undetected in all vertical and radial growth phase cases Interestingly, 13 out of 13 of the lymph node metastasis expressed extremely high levels of COX-2 in overlying epithelium and inflammatory cells, and COX-2 was strongly detected in the metastatic cancer cells per se. For additional information on the expression of COX-2 in malignant melanoma, we determined the expression of COX-2 protein in several different melanoma cell lines. We found that 3We found that 5 out of 7 of the melanoma cells over expressed COX-2 compared to normal melanocytes. Collectively, these data suggest that COX-2 may play a functional role in metastases of melanoma, and treatment with COX-2 inhibitors may be efficacious for malignant melanoma.
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PMID:Analysis of cyclooxygenase 2 (COX-2) expression during malignant melanoma progression. 1468 83


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