Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients entered into phase II trials in metastatic malignant melanoma should be carefully selected in order to ensure that they live long enough to permit a meaningful evaluation of the efficacy of a given drug. In this selection emphasis has been put on performance status. However, also for patients with a good performance status, survival is often short. The purpose of this study has been to identify supplementary prognostic factors as these could be of help in the design of phase II trials. From 1978-1986, 177 consecutive patients were given various chemotherapy regimens for metastatic malignant melanoma in the Norwegian Radium Hospital. About 92% had a performance status of ECOG 0-2. Median survival was 4.0 months (0-30 months). Multivariate survival analysis selected lactate dehydrogenase (LDH) greater than 450 U/l, presence of brain metastases, leukocyte count greater than 10 x 10(9)/l, and erythrocyte sedimentation rate (ESR) greater than 15 mm/h as significant prognostic factors indicating short survival with low probability of surviving 3 months. Patients with normal values of LDH, leukocyte count, and ESR had a median survival of 11.5 months with 94% surviving 3 months. We conclude that this information could have an impact on the design of phase II trials.
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PMID:Regression analyses of prognostic factors in metastatic malignant melanoma. 276 10

The blood-brain barrier presents a major obstacle to the systemic treatment of malignant brain tumors and brain metastases. We investigated whether the direct injection of liposomes into the internal carotid artery of normal mice or mice with experimental brain-melanoma metastases could allow delivery of anticancer drugs across this barrier. Liposomes of different sizes (greater than 5 microns, less than 1 micron, 40-80 nm) and lipid compositions were injected i.v. or into the internal carotid artery. The retention of liposomes in the brain of normal C3H/HeN mice was similar to that observed in mice with experimental brain cancer metastasis. The highest accumulation of liposomes in the brain occurred with large multilamellar vesicles, which also produced severe toxicity presumably due to embolism. Smaller liposomes were not toxic but did not accumulate in the brain. Liposomes injected i.v. did not accumulate in the brain, either. Thus, neither i.v. nor intracarotid administration of liposomes produce results suitable for therapy of brain tumors/metastases.
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PMID:Arrest and retention of multilamellar liposomes in the brain of normal mice or mice bearing experimental brain metastases. 277 29

Re-irradiation for recurrent manifestations of brain metastases has been reported to be of benefit by either increasing the duration of survival or improving the quality of life. The records of 455 patients with brain metastases treated by radiation therapy at the University of Colorado Health Sciences Center from 1975 through 1986 were reviewed. Of these, 44 patients (9.7%) were re-irradiated because of suggestive neurological findings and/or imaging studies diagnostic of recurrent disease. The primary site distribution was as follows: lung (non-small cell)--15 (34%), lung (small cell)--9 (20%), melanoma--5 (11%), breast--4 (9%), genitourinary--4 (9%), unknown--4 (9%), lymphoma--2 (4%), and endometrium--1 (2%). Retreated patients received at least two courses of irradiation and one received three. The median interval between the first and second courses was 34 weeks (7.8 months). For the initial course of treatment, all patients were treated to the whole-brain with megavoltage X rays to a dose of 30-36 Gy (median 30 Gy) at 1.5 to 4.0 Gy/fraction (median 3.0 Gy/fraction). Retreatment also consisted of whole-brain irradiation (37/42 patients) to additional doses of 6-36 Gy (median 25 Gy) at 2.0 to 4.0 Gy/fraction (median 3.0 Gy/fraction). The total cumulative doses to the brain, therefore, varied from 38-75 Gy with a median of 60 Gy. Survival data were available for 42 of 44 patients retreated. All patients died with disease. The overall median survival following the initial course of irradiation was 40 weeks (9.2 months) with 10 patients (24%) living beyond 1 year. The median survival following retreatment, however, was only 8 weeks with one patient surviving greater than 1 year. Only 12 patients (27%) showed partial neurological improvement with re-irradiation and over one-half (55%) either failed to respond or deteriorated during or soon following retreatment. Brain necropsies were performed in 8 patients. Three of these had developed brain necrosis and two most likely died as a direct consequence. It is concluded that retreatment of brain metastases is seldom worthwhile. Survival is usually short and most importantly, the quality of survival frequently is not improved.
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PMID:Brain metastases: results and effects of re-irradiation. 284 Dec 66

Four of five patients with brain metastases from melanoma had increased lofetamine I 123 uptake in the region of the tumor deposits. A comparison group of five patients with melanoma with no clinical or radiologic evidence of brain involvement and 46 of 47 patients without malignant melanoma but with known brain tumors of other histologic types had normal or decreased iofetamine I 123 brain uptake in the region of the tumor. An exception was one patient whose metastatic small cell lung cancer to the brain showed focally increased uptake. These findings suggest that certain brain tumors such as melanoma are capable of selectively binding iofetamine I 123 because of specific chemical properties of the radiopharmaceutical. Increased uptake of iofetamine I 123 in brain lesions in a patient at risk for metastatic melanoma may be a useful aid to differential diagnosis.
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PMID:Increased iofetamine I 123 brain uptake in metastatic melanoma. 284

Subcutaneous tumors initiated with mouse B16 melanoma clones G3.5 and G3.12 disseminated visible spontaneous brain metastases in 67 per cent and 32 per cent, respectively, of mice with extensive lung metastasis. Most brain metastases appeared as pigmented emboli within blood vessels of the leptomeninges overlying the cerebral cortex. Intravascular metastases consisted of tumor cell aggregates surrounded by fibrous material and generally contained viable cells that proliferated in culture. Some metastatic emboli apparently proliferated intravascularly to such an extent as to cause vessel disruption, permitting tumor invasion into the adjacent cerebral cortex. Cultured cells from G3.12 leptomenings metastases produced tumors that metastasized to a much greater extent than unselected G3.12 tumors, but brain metastasis still occurred only secondarily, after initial dissemination to the lungs. In contrast, G3.5 brain metastasis-derived populations formed tumors that ultimately metastasized to the brain to lesser extents than did unselected G3.5 tumors. One selected variant, G3.12/BM2, reproducibly formed visible and viable brain metastases in more than 80 per cent of tumor-bearing mice, and lethal or potentially lethal brain metastases in 10-15 per cent of mice. This variant may serve as a model for clinical brain metastasis.
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PMID:B16 melanoma spontaneous brain metastasis: occurrence and development within leptomeninges blood vessels. 290 27

The proliferation rate of 40 intracranial neoplasms (30 gliomas, 1 hemangioblastoma, 3 meningiomas, 1 neurinoma and 5 brain metastases) was investigated using the monoclonal antibody Ki-67. In eleven of the gliomas recurrences could be observed, and two of them recurred for second time. In total the Ki-67 labelling indices of 53 specimens were investigated. The Ki-67 nuclear antigen was demonstrated in frozen sections by application of the appropriate monoclonal antibodies according to a modified alkaline phosphatase-antialkaline phosphatase (APAAP) technique. The proliferation rate was evaluated by cell count calculation of the staining index. Ki-67-labelled glioma cells varied from 0.2 percent in one meningioma (WHO-grade I) to 9.1 percent in one glioblastoma. In ten glioma recurrences, higher Ki-67 staining indices could be observed than in their primaries, even when the histological grading did not change substantially. In a cerebellar hemangioblastoma, a trigeminal neurinoma and two endotheliomatous meningiomas the fraction of stained nuclei was less than one percent; however, one recurrent transitional meningioma without any histological sign of malignancy showed a staining index of 2.4 percent. The staining indices of five brain metastases of different malignancies ranged from 1.5 percent in a malignant melanoma to 6.1 percent in bronchial carcinoma. In the majority of the cases examined, the percentage of Ki-67 labelled cells was in accordance with the histologic grade of the neoplasm. In general, there was a direct relationship between the number of stained nuclei and the frequency of mitoses (mitotic index) evaluated in hematoxylin-eosin stained frozen sections. Interestingly, the frequency of mitosis and stained nuclei were higher in tumor recurrences than in the primaries. The results of this study imply that immunohistological labelling of the proliferating cell fraction should become an important additional criterion to predict the biological behaviour of human nervous system neoplasms.
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PMID:Relationship between Ki-67 positive cells, growth rate and histological type of human intracranial tumors. 305 45

Amongst 15,000 autopsies performed between 1969 and 1984 in the Department of Pathology of the University Hospital of Innsbruck (Austria) 237 cases (1.6%) with brain metastases were found. The mean age of patients was 61.2 years and 148 patients out of 230 cases with satisfactory records were male (64.3%). Multiple lesions were found in 58%. In absolute figures carcinoma of the lung, followed by malignant melanoma and breast carcinoma were, as in other series, the most frequent primary site for brain metastases. The relative frequency of brain metastases in various anatomical regions of the brain showed that malignant melanoma tends to metastasize to the frontal and temporal lobes, breast carcinoma to the cerebellum and the basal ganglia, large cell carcinoma of the lung to the occipital lobe and squamous cell carcinoma of the lung to the cerebellum. Metastases of small cell carcinoma of the lung were found equally distributed in all regions of the brain. Our study supports the results of several experimental investigations, suggesting the possibility that specific cell surface properties of metastasizing tumour cells and particular properties of the vascular endothelium of the target organs of metastasis are responsible for the location of metastases. The results of this study suggest that there are substantial differences in regard to these properties even within one target organ.
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PMID:Site preference of metastatic tumours of the brain. 312 19

Cell lines were obtained from three malignant melanoma patients by culturing cell suspensions from tumor biopsies. A total of six lines (I to VI) were established. One line each was established from the first two cases. Lines III and IV were established from two different methyl cellulose colonies derived from the primary tumor of case 3; line III was from a non-pigmented and line IV from a pigmented colony. Cloning of line IV resulted in two highly malignant (IV Cl 1 and IV Cl 3) and one less malignant (IV Cl 2) clone. Clone IV Cl 1 was inoculated intracardially in nude mice and gave rise to adrenal and brain metastases. Lines V and VI were derived from such metastases. Multiple structural and/or numerical chromosome abnormalities were detected in all lines. Line I had 57-61 chromosomes, with structural changes affecting 1p, 2p, 3q, 7p, 7q, 11p, 14q, 17q, and 22q, as well as one unidentified marker. Line II had 40-48 chromosomes, with structural changes of 1p, 1q, 4q, 5p, 6p, 8p, 11p, 11q, 14p, 20p, and two unidentified markers. Line III had 45 chromosomes, 6q+, del(11p), and a centric fusion between chromosomes 14 and 15. Line IV had 45-46 chromosomes. The clonal changes included rearrangements of 1p, 9p, 11p, and the centric fusion of chromosomes 14 and 15. Line V was pseudodiploid and contained aberrations of 1p, 9p, 11p, 14q, 20q, an isochromosome for 21q, and an unidentified marker. Finally, the pseudodiploid line VI had changes of 9p, 11p, centric fusion of chromosomes 14 and 15, and an unidentified marker. Although no single identical aberration was shared by all six lines, structural abnormalities of 11p were invariably present and, hence, might constitute a common cytogenetic feature in melanoma development. The most consistent difference between the amelanotic and melanotic lines derived from case 3 was the presence of a 6q+ marker in the former and a 9p+ marker in the latter.
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PMID:Multiple karyotypic abnormalities, including structural rearrangements of 11p, in cell lines from malignant melanomas. 318 9

Conventional therapy for solitary brain metastases includes radiotherapy and surgical resection in selected cases. Often, however, the metastasis recurs and limits the quality of life and survival of the patient. Once the metastasis recurs, therapeutic options are limited. Brachytherapy delivers a high total dose of radiation to a localized area, allowing reirradiation at the time of recurrence. Three patients with recurrent brain metastases treated with iridium-192 implants are presented; two of these patients had breast carcinoma and one had malignant melanoma. The implants allowed long term survival in the two patients with recurrent metastatic breast carcinoma. Unfortunately, the patient with melanoma did not respond to the brachytherapy and died within 7 months of implantation. The approaches to treatment to metastatic brain tumors and the rationale for using brachytherapy are discussed.
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PMID:Brachytherapy in the treatment of recurrent solitary brain metastases. 321 71

The purpose of this study was to examine the nature of the blood-brain barrier in experimental brain metastases. Syngeneic fibrosarcoma or melanoma cells were injected into the internal carotid arteries of mice. Several weeks later, once the experimental brain metastases were established, the mice were given injections iv of sodium fluorescein. The capillaries within the metastatic foci were enlarged and irregular, but there was no leakage of sodium fluorescein, showing that the blood-brain barrier was intact. The neoplastic lesions were infiltrated by mononuclear phagocytes, which were identified by immunohistochemical localization of the macrophage-specific antigen F4/80, class II major histocompatibility complex (MHC) antigens, and the macrophage product interleukin-1 (IL-1). The metastatic foci contained numerous stellate macrophages that expressed F4/80 and MHC class II antigens, but little IL-1. Round, monocyte-like F4/80 and MHC class II-positive cells were also observed within the tumor lesions and adhering to walls of the tumor microvasculature. Mice with fibrosarcoma brain metastases also had edematous lesions at sites remote from the metastatic foci that contained numerous astrocytes expressing class II MHC but not F4/80 antigens. In conclusion, the blood-brain barrier is intact within experimental brain metastases, yet macrophages of blood monocyte origin can infiltrate the lesions.
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PMID:Macrophage infiltration into experimental brain metastases: occurrence through an intact blood-brain barrier. 326 1


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