Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Cutaneous neurocristic hamartomas (CNH) are pigmented lesions of neural crest origin that involve the skin and superficial soft tissue. They consist of a complex proliferation of nevomelanocytes, schwann cells, and pigmented dendritic and spindled cells. Malignancies can arise within the lesions, but few studies have dealt with this issue. We studied seven cases of CNH in which malignancy supervened. They included four congenital and three acquired lesions that involved the head and neck (five cases) or back (two cases) in patients aged from 11 to 67 (mean, 32) years. Malignant tumors developed 15 to 67 (mean, 32) years after identification of the pigmented lesion in the congenital CNH and after 1 to 6 (mean 3.5) years in the acquired CNH. The malignant tumors had a deep intradermal or subcutaneous origin and lacked a junctional component. Most were circumscribed, multinodular, melanin-containing tumors composed of bland, small, rounded to spindled cells, focally displaying a trabecular or nested growth pattern. Nuclear palisading and perivascular pseudorosettes were present in several tumors. In two examples, the neoplasm consisted predominantly of large pleomorphic epithelioid cells. Tumors contained immunoreactive S-100 protein (all of seven cases), a melanoma-associated antigen (HMB-45)( five of six cases, neuron-specific enolase (five of seven cases) and vimentin (six of six cases). The four patients with congenital lesions tended to have multiple recurrences and died of disease after 2 to 20 (mean, 9) years, three with metastases, one with direct invasion of the posterior fossa. The three patients with acquired lesions are alive after 1 to 5 years two with persistent disease. In contrast to common melanomas, these tumors have a propensity to recur as bulky nodules and to metastasize after many years or decades. Because these tumors exhibit melanocytic differentiation and arise in hamartomatous lesions composed of neural crest derivatives, we have designated them cutaneous malignant melanotic neurocristic tumors.
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PMID:Cutaneous malignant melanotic neurocristic tumors arising in neurocristic hamartomas. A melanocytic tumor morphologically and biologically distinct from common melanoma. 865 45

Follow-up data of more than 300 melanoma patients were reviewed in which an immunoscintigraphy study had been performed as part of a routine staging protocol. All patients had received a commercially available 99mTc-labeled F(ab')2 fragment specific to a high-molecular-weight melanoma-associated antigen (HMW-MAA). Survival data of patients that had received one injection (group I) were compared with those receiving two or more injections (group II). For better comparison, patients were matched according to the following risk factors: (i) age, (ii) sex, (iii) tumor level according to Clark, (iv) tumor depth according to Breslow, (v) location of primary tumor, and (vi) metastases [and if positive, (vii) location of metastases]. Twenty-eight patient pairs were established that showed no statistically significant differences comparing the above-mentioned risk factors. In addition, no significant difference was found comparing the interval between primary diagnosis of disease and first injection of monoclonal antibody (MAb) in both groups. In contrast, survival time between first diagnosis of melanoma was significantly prolonged in group II (multiple injections) as compared to group I (single injection). This was true for survival time between primary diagnosis as well as from first injection of MAb until death or closing time of study. Our data suggest, that multiple injections of melanoma-specific F(ab')2 fragment have a beneficial effect on median survival in melanoma patients.
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PMID:Effects of diagnostic application of monoclonal antibody on survival in melanoma patients. 908 31

We compared the immunogenic activity of irradiated vaccines prepared from B16 F10 melanoma cells with one made from B16 F10 melanoma cells transfected with genes encoding murine IL-2 or GM-CSF. Vaccines were studied in the conditions of treatment of C57BL/6 mice with or without the corresponding lymphokines. Control and prevaccinated mice were challenged with parental B16 F10 murine melanoma cells (5 x 10(5)) subcutaneously in the midtail to examine growth of the primary (local) tumor in the middle of the tall and metastases to the lungs. This experimental model is very close to the clinical stages of metastatic melanoma. The effectiveness of preimmunization of mice was determined by the levels of antibody production to a melanoma-associated antigen termed B700. The comparison of antibody production, growth of primary melanoma tumors, number of mice surviving at the end of the observation period, mean survival time and per cent mice with metastases in the lungs showed that the best course of immunotherapy was prevaccination of mice with a vaccine of irradiated B16 F10 melanoma cells transfected to secrete GM-CSF, coupled with GM-CSF therapy.
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PMID:Immunization of mice with irradiated melanoma tumor cells transfected to secrete lymphokines and coupled with IL-2 or GM-CSF therapy. 941 96

The aim of the study was to evaluate single-injection gamma probe-guided sentinel lymph node (SLN) detection, applied in 40 melanomatous selective sentinel lymphadenectomies (SSLNDs). Thirty-four patients underwent preoperative lymphoscintigraphy, intraoperative SLN identification by a gamma-detecting probe and blue dye, and SLN sampling. The first 11 patients underwent formal lymphadenectomy. The following 23 patients underwent formal lymphadenectomy only when the SLN was involved with tumor. Evaluation included hematoxylin-eosin-stained slide microscopy, monoclonal antibodies to S-100 protein, and the melanoma-associated antigen HMB45. In all patients, single or multiple SLNs were identified by the gamma-detecting probe. However, only 82.5% of these specimens included blue-stained nodes. None of the non-SLN specimens were the exclusive site of metastases. Four patients had metastases in their SLN specimen without non-SLN involvement. We conclude that SSLND can be performed easily and precisely with the exclusive use of the gamma-detecting probe. A single injection is feasible, and decreases operating room contamination and patient discomfort.
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PMID:Single-injection gamma probe-guided sentinel lymph node detection in 40 melanomatous lymphadenectomies. 978 20

The goal of experimental clinical protocols using peptide antigen for active vaccination and treatment of patients with metastatic cancer is to induce a vigorous cytotoxic T lymphocyte (CTL) response against the immunizing antigen, and thereby against tumor cells expressing the antigen. However, the magnitude and breadth of human CTL responses induced by peptide immunization, and in particular against antigens expressed by normal tissues as well as tumors, is not well characterized. This issue was examined by characterizing CTL cloids derived from peripheral blood mononuclear cells of three patients who received peptide immunization as treatment for metastatic melanoma. All patients received G9-209-2M peptide, a modified epitope of the gp100 melanoma-associated antigen. The results indicated that the CTL response induced by this peptide antigen was highly heterogeneous both in terms of avidity toward the peptide antigen and recognition of tumor cell lines. Furthermore, avidity of each CTL cloid for the native peptide was highly predictive of tumor reactivity. These results are discussed in terms of their implications for peptide vaccination and adoptive tumor immunotherapy.
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PMID:Antitumor immunization with a minimal peptide epitope (G9-209-2M) leads to a functionally heterogeneous CTL response. 1040 30

Histocompatibility leukocyte antigen (HLA)-A2 is used as a restricting element to present several melanoma-associated antigen (MAA)-derived peptides to cytotoxic T lymphocytes (CTLs). HLA-A2 antigen is selectively lost in primary melanoma lesions and more frequently in metastases. Only scanty information is available about the molecular mechanisms underlying this abnormality, in spite of its potentially negative impact on the clinical course of the disease and on the outcome of T cell-based immunotherapy. Therefore, in this study we have shown that the selective HLA-A2 antigen loss in melanoma cells 624MEL28 is caused by a splicing defect of HLA-A2 pre-mRNA because of a base substitution at the 5' splice donor site of intron 2 of the HLA-A2 gene. As a result, HLA-A2 transcripts are spliced to two aberrant forms, one with exon 2 skipping and the other with intron 2 retention. The latter is not translated because of an early premature stop codon in the retained intron. In contrast, the transcript with exon 2 skipping is translated to a truncated HLA-A2 heavy chain without the alpha(1) domain. Such a polypeptide is synthesized in vitro but is not detectable in cells, probably because of the low steady state level of the corresponding mRNA and the low translation efficiency. These results indicate that a single mutational event in an HLA class I gene is sufficient for loss of the corresponding allele. This may account, at least in part, for the high frequency of selective HLA class I allele loss in melanoma cells. Our conclusion emphasizes the need to implement active specific immunotherapy with a combination of peptides presented by various HLA class I alleles. This strategy may counteract the ability of melanoma cells with selective HLA class I allele loss to escape from immune recognition.
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PMID:Selective histocompatibility leukocyte antigen (HLA)-A2 loss caused by aberrant pre-mRNA splicing in 624MEL28 melanoma cells. 1043 84

Malignant melanoma is one of the most frequent malignancies of the skin. This is particularly true of malignant melanoma in juveniles. Its incidence has more than doubled from the 1970s to the mid-1990s. Presently, 15 new cases are recorded per 100,000 inhabitants a year in Germany. At Fachklinik Hornheide, a tumor center specializing in skin neoplasm with patients being referred from all over Germany, the number of melanoma patients treated per year has been approximately 500-550 for the past 10 years. In the present study, the state-of-the-art therapy for primary melanoma and treatment of the regional lymph node system is discussed. The radical treatment formerly advocated with wide tumor resection plus radical neck dissection is no longer justified for this immunogenic malignant tumor caused by endogenic as well as exogenic factors. "Sentinel lymph node" imaging by means of radioactive substances for diagnosing possible melanoma metastases in adjacent lymph nodes has changed the therapeutical concept. Tumor staging by means of ultrasound, CT, MRT, or PET allows the differentiation of tumors without distant metastases and a favorable prognosis, from melanomas which have to be considered as generalized disease. In addition to surgical resection of the tumor and neck dissection for removal of lymph nodes, adjuvant immunotherapy with interferon-alpha is capable of prolonging survival without a recurrence. Palliative chemotherapy or immunotherapy are valuable options for cases with generalized melanoma. Vaccination with a melanoma-associated antigen or dendritic cells is at an experimental stage and may become part of future treatment strategies.
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PMID:[Malignant melanoma in the area of the head and neck]. 1093 58

The presence of circulating tumor cells in bone marrow and peripheral blood of cancer patients may reflect the aggressiveness of the disease. This also applies to cancers that rarely give rise to overt bone marrow metastases. The clinical validity of micrometastasis detection for staging and prognostication depends on the sensitivity and reliability of the detection method. In malignant melanoma, most studies have used reverse transcriptase polymerase chain reaction (RT-PCR) techniques, commonly with tyrosinase mRNA as the target molecule. Unfortunately, highly inconsistent results have been reported, raising doubts about this approach. In a study of 81 melanoma patients with metastatic disease, we used an immunobead rosetting method in which live melanoma cells are selected and identified by binding of paramagnetic beads coated with the 9.2.27 antibody against the high molecular weight melanoma-associated antigen. In bone marrow samples obtained from 60 patients, 14 (23.3%) were positive, compared to only two of 81 in blood. A highly significant correlation (p = 0.0001, log rank test) was found between micrometastasis positivity and overall survival from time of removal of the primary tumor. Moreover, in regression analysis it was found that the presence of micrometastatic cells was an independent and the most important indicator of poor prognosis, with a relative risk of 5.38. The immunomagnetic method is simple, rapid, and highly sensitive and will be used in further prospective clinical studies.
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PMID:Immunobead-based detection and characterization of circulating tumor cells in melanoma patients. 1109 32

In this study, we investigated whether maturation of monocyte-derived myeloid dendritic cells (DCs) is differentially affected by the uptake of dying human melanoma cells in distinct phases of apoptosis. Maturation of monocyte-derived DCs, as documented by phenotype analysis and T-cell immunostimulatory activity, was inhibited by phagocytosis of dying melanoma cells containing a large fraction of cells in early apoptosis (Annexin-V+ and propidium iodide-) but promoted by the same tumors when in late apoptosis/secondary necrosis (Annexin-V+ and propidium iodide+) or when dying by primary necrosis. These opposite effects on DC maturation were observed after the uptake of early or late apoptotic cells from most vertical growth phase primary tumors and all metastases but not after the uptake of dying cells from a radial growth phase primary tumor or normal adult melanocytes. Inhibition of DC maturation by early apoptotic melanoma cells correlated with expression of interleukin-10 in neoplastic cells and was prevented by preincubating the tumor cells with a neutralizing antibody to interleukin-10 before tumor uptake by DCs. Cross-presentation of the melanoma-associated antigen gp100(209-217) to peptide-specific CTLs by HLA-A*0201+ DCs was achieved 48-72 h after phagocytosis of HLA-A*0201- melanoma cells in apoptosis, or primary necrosis, but only when tumor necrosis factor-alpha was added to DCs 4 h after the initiation of tumor phagocytosis. These results suggest that phases of apoptosis and neoplastic transformation affect maturation of myeloid DCs that take up dying cells of the melanocyte lineage. However, neoplastic cells in late apoptosis, or even in primary necrosis, induce only a partial DC differentiation not sufficient to achieve cross-presentation of tumor antigens to CTLs unless further DC maturation is promoted by additional signals. These results suggest a novel mechanism of tumor escape that may prevent the development of antitumor immunity through the maturation block induced in DCs by neoplastic cells in the early phase of apoptosis.
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PMID:Phases of apoptosis of melanoma cells, but not of normal melanocytes, differently affect maturation of myeloid dendritic cells. 1171 53

The lack of melanoma-associated antigen (MAA) expression has been associated with the reduced overall survival in melanoma patients. In order to investigate whether the MAA expression detected on cell cultures established from melanoma patients might relate to the overall survival in these patients, we screened primary cell cultures derived from 37 melanoma metastases for the expression of five known MAA: Melan-A, tyrosinase, gp-100, MAGE-1 and MAGE-3 by polymerase chain reaction (PCR) and fluorescence-activated cell sorting (FACS). MAA expression detected by PCR was found at a high percentage in evaluated melanoma cell lines: 25 of 28 (89%) were positive for Melan-A, 22 of 28 (79%) were positive for tyrosinase, 26 of 28 (93%) were positive for gp-100, and 18 of 28 (64%) were positive for MAGE-3 expression. Using the FACS method the percentage of MAA-positive cell lines was much lower: 14 of 31 (45%) cell lines were positive for Melan-A, eight of 31 (26%) were positive for tyrosinase, 13 of 31 (42%) were positive for gp-100, six of 31 (19%) were positive for MAGE-1, and 14 of 31 (45%) were positive for MAGE-3 expression. Kaplan-Meier survival analysis demonstrated that the patients whose cell lines were positive for Melan-A expression by PCR had significantly longer overall survival time as Melan-A PCR-negative cases (P=0.0038). This could not be shown for any of the markers tested by FACS. Our results suggest that the expression of Melan-A/MART-1 in patient-derived cell cultures may help to identify a group of melanoma patients with prolonged survival.
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PMID:Expression of Melan-A/MART-1 in primary melanoma cell cultures has prognostic implication in metastatic melanoma patients. 1530 55


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