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)

In the management of patients with primary malignant melanoma of the uvea, treatment techniques have included not only enucleation but also photocoagulation, cryotherapy, photoradiation, a limited resection, as well as circumstances indicating exenteration of the orbit. Surgical management has been the primary treatment program for over 100 years. In a compilation of nine reported series consisting of 2,024 enucleations, the five- and ten-year survivals following surgery were 63% and 43%, respectively. The 25-year survival has been reported to be 40%. In 1974 at Wills Eye Hospital and Hahnemann University, the cobalt-60 plaques technique was introduced. During the following years, other radioactive isotopes were introduced including iridium-192, iodine-125, ruthenium-106/rhodium-106 and more recently palladium-103. At the present time, iodine-125 is the most widely used radionuclide. Until now, 302 patients treated with plaque brachytherapy showed an actuarial survival of 77% and 67.8% at five and eight years, respectively. There was no significant survival difference when compared with a similar group of patients undergoing enucleation. Other retrospective studies show similar excellent results. In spite of these convincing results, the decision making process in management melanoma remains unsettled primarily due to the absence of prospective randomized trials. Because of this, the Collaborative Ocular Melanoma Study was initiated. From the standpoint of toxicity, the data are available on ocular radiation toxicity. In an analysis of 77 patients from the Wills Eye Hospital with pretreatment visual acuities of 20/25 or better, it was noted that 90% of patients who had received less than 500 Gy to the fovea retained visual acuity of 20/200 or better while only 52% of patients receiving more than 5,000 Gy to the fovea had vision of 20/200 or better. A serious late effect of radioactivity plaque treatment is scleral necrosis which may require repair or enucleation even in the absence of tumor progression. Enucleation may be necessary in approximately 10% of patients. We conclude that malignant melanoma of the uvea can be safely treated with radioactive plaques.
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PMID:Brachytherapy of choroidal melanomas. 154 47

The use of non-radioactive in situ hybridization (ISH) with chromosome-specific repetitive DNA probes to study genomic changes, aneuploidy, and heterogeneity during melanocytic tumor progression, relies on its applicability to non-mitotic interphase nuclei, present in cell suspensions and tissue sections. Therefore, we studied the feasibility of detecting numerical aberrations with respect to the (peri-) centromere regions of chromosomes 1 and 7 in intact nuclei of two human melanoma cell lines with different metastatic behavior in nude mice. In addition, we used paraffin sections from xenograft lesions, obtained by inoculation of these cell lines in nude mice (subcutaneous tumors and spontaneous lung metastases). Paraffin sections from the original primary cutaneous melanoma (with a subepidermal and a dermal part) and two loco-regional metastases were also studied, one of which was the source for the cell lines. These cells and tissues represent examples of materials used in different approaches to the study of melanocytic tumor progression. Regarding the targeted sequences, ISH analysis showed that both cell lines were heterogeneous and aneuploid. The results correlated well with those obtained by ISH on metaphase spreads. Differences between the lines, which could not be detected by flow-cytometric or conventional karyotyping analysis, included data suggestive of a polyploid subpopulation and an extra copy of chromosome 7 in the metastasizing cell line. The polyploid population could be detected also in the paraffin sections of the corresponding subcutaneous xenografts and lung metastases in the mice. Both areas in the patients' primary melanoma could be evaluated separately and showed similar supernumerary aberrations of the chromosome-specific targets. These abnormalities matched those found in both metastases. Our results demonstrate that ISH can be used to visualize genomic abnormalities at the single-cell level in melanocytic nuclei in their natural context, which makes it a promising tool in the histopathology of melanocytic lesions and in the study of melanocytic tumor progression.
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PMID:In situ detection of supernumerary aberrations of chromosome-specific repetitive DNA targets in interphase nuclei in human melanoma cell lines and tissue sections. 154 28

Thirty-one patients with disseminated melanoma or renal cell cancer (RCC) who had a limited relapse or persistent disease after a partial or complete response to interleukin-2 (IL-2)-based immunotherapy underwent resection of progressing tumors or residual sites of disease. There were no surgery-related deaths. The median time to disease progression after resection for patients with RCC (n = 16) and melanoma (n = 15) was 11 and 5 months, respectively. All patients with melanoma had tumor progression within 10 months of surgery. Seven of 16 patients with RCC were free of tumor progression 4 to 44 months after surgery. Three of 12 patients with RCC rendered disease-free by surgery remain disease-free after 2 years. These data suggest that surgical resection is a reasonable option in selected patients who have a relapse after responding to IL-2-based immunotherapy. Although this retrospective study could not determine the relative survival benefits of surgery and immunotherapy, it showed that resection of metastatic disease after a response to immunotherapy can result in significant disease-free survival in patients with RCC but not melanoma.
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PMID:Surgical resection of metastatic renal cell carcinoma and melanoma after response to interleukin-2-based immunotherapy. 155 Oct 67

Different results have been reported on the expression of epidermal growth factor receptor (EGFR) in human melanocytic lesions, which may be due to different methodologic approaches. Therefore, we compared EGFR expression in six human melanoma cell lines by utilizing the monoclonal antibodies 2E9, 425, and 225, applying four immunocytochemical staining procedures. The results were compared with those obtained by a multiple point ligand binding assay. In addition, Northern blot analysis was performed. A three-step immunoperoxidase method using the monoclonal antibody 2E9 proved most sensitive. Staining intensities, estimated semiquantitatively, correlated well with the quantitative data obtained by the ligand-binding assay. Expression on the mRNA level was also in agreement with these results. Immunohistochemical staining of a large series of human cutaneous melanocytic lesions using the method selected showed differential EGFR expression in various stages of melanocytic tumor progression: 19% of common nevocellular nevi; 61% of dysplastic nevi, 89% of primary cutaneous melanomas, and 91% of melanoma metastases showed staining of the melanocytic cells. Intralesional heterogeneity of EGFR expression was present. Although the mean percentage of positive melanocytic cells in positive lesions did not increase with progression, mean staining intensity was stronger in malignant lesions compared to benign lesions. Ligand binding assays showed that EGFR expression in the highly metastasizing cell lines MV3 and BLM was at least 40 times higher than in the cell lines IF6, 530, M14, and Mel57, which do not or only sporadically metastasize after subcutaneous inoculation in nude mice. Although the differences between the various stages of progression are not absolute, we provide further evidence that EGFR expression increases in human melanocytic tumor progression.
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PMID:Increasing epidermal growth factor receptor expression in human melanocytic tumor progression. 162 28

To define the role of stereotactic radiosurgery in the treatment of metastatic brain tumors we treated 24 consecutive patients (20 men, 4 women) with the 201-source 60Co gamma unit between May 1988 and March 1990. The primary tumors included malignant melanoma (n = 10), non-small cell lung carcinoma (n = 6), renal cell carcinoma (n = 3), colorectal carcinoma (n = 1), oropharyngeal carcinoma (n = 1), and adenocarcinoma of unknown origin (n = 3). All tumors were less than or equal to 3.0 cm in greatest diameter. Twenty patients received a planned combination of 30-40 Gy whole brain fractionated irradiation and a radiosurgical "boost" of 16-20 Gy to the tumor margins; one patient refused conventional fractionated irradiation. Three patients with recurrent, persistent, or new non-small cell lung carcinomas had radiosurgical treatment 12-20 months after receiving 30-42.5 Gy whole-brain external beam irradiation. Stereotactic computed tomographic imaging was used for target coordinate determination and imaging-integrated dose planning. All tumors were enclosed by the 50-90% isodose shell using one (n = 22), two (n = 1), or three (n = 1) irradiation isocenters. During this 23-month period (median follow-up of 7 months) no patient died from progression of a radiosurgically-treated brain metastasis. Ten patients died of systemic disease (n = 8) or remote central nervous system metastasis (n = 2) between 1 week and 10 months after radiosurgery. One patient had tumor progression and underwent craniotomy and tumor excision 5 months after radiosurgery. To date, median survival after radiosurgery has been 10 months; 1-year survival was 33.3%. Stereotactic radiosurgery eliminated the surgical and anesthetic risks associated with craniotomy and resection of solitary brain metastases. Radiosurgery also effectively controlled the growth of tumors considered "resistant" to conventional irradiation.
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PMID:Radiosurgery for solitary brain metastases using the cobalt-60 gamma unit: methods and results in 24 patients. 164 95

Although the incidence of, and deaths due to, malignant melanoma are rising at a rapid rate, few experimental models mimic the highly metastatic properties associated with the pathogenesis of the human disease, making study of the disease difficult. Thus, new human models are required to understand melanoma biology, especially its metastatic properties. Here we describe C8161, a highly invasive and spontaneously metastatic human melanoma cell line, which grows progressively in the subcutis of athymic nude mice with an average doubling time of approximately 6 days. By the time the tumor reaches a diameter of 1 cm, amelanotic metastases in lymph nodes, skin, peritoneal wall, spleen and lungs have formed. By comparing C8161 to variants from other well-characterized human malignant melanomas (A375 and MeWo) with differing metastatic traits, properties presumed to be involved in metastatic propensity were examined. C8161 showed a 2- to 14-fold higher ability to invade reconstituted basement membrane barriers in the MICS and correspondingly high type-IV collagenase mRNA levels and collagenolytic activity, as compared with other melanoma cell lines. Likewise, differential adhesion to immobilized RBM or HUVEC monolayers was observed, but did not correlate to rank orders of malignant properties. Recently, a correlation between surface expression of ICAM-1 and secondary tumor formation by human melanomas has been described in several laboratories. Basal levels of ICAM-1 on C8161, A375 and MeWo human melanomas were compared, but no correlation with metastatic potential was noted. Proto-oncogene expression in C8161 cells was compared with A375P and A375M variants using Northern blot analysis. c-myc expression was 6-fold greater than both A375 variants; c-fos expression was 3.4-fold less than A375P and 1.7-fold less than A375M; c-jun in C8161 cells was 2.5-fold and 2.1-fold greater than expression in A375P and A375M, respectively. Because C8161 is so highly malignant, amenable to experimental manipulation, and its behavior in nude mice mimics the clinical course of malignant melanoma, this cell line will prove valuable for studying properties associated with human melanoma tumor progression.
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PMID:Characterization of a highly invasive and spontaneously metastatic human malignant melanoma cell line. 167 Oct 30

Advanced steps of tumor progression are generally characterized by an increased growth fraction within the neoplastic cell population. The presence of a relevant growth fraction is also related to widely accepted prognostic parameters in some human malignancies. Our aims were to evaluate the presence of a growth fraction with Ki67 monoclonal antibody (MoAb), and to correlate it with tumor progression and HLA-DR antigen expression in 88 melanocytic lesions. The lesions were 19 acquired melanocytic nevi, 58 primary melanomas [divided into 26 superficial spreading melanomas (SSM), 24 superficial spreading melanomas with nodular areas (SS + NM), and five nodular melanomas (NM)], and 11 metastases from malignant melanomas. Ki67 MoAb stained 16%, 19%, 71%, 100%, and 82% of nevi, SSM, SS + NM, NM, and metastases, respectively. Among primary melanomas, Ki67 MoAb stained 12%, 28%, 50%, and 70% of tumors less than 0.75, 0.75-1.49, 1.5-2.9, and greater than or equal to 3 mm thick, respectively. A concordant reactivity pattern for Ki67 and HLA-DR antigens was found in 72% of lesions (p less than 0.0001). We have shown that a representative growth fraction (ie, Ki67 reactivity) is present in melanocytic lesions only in advanced steps of tumor progression and correlates with HLA-DR antigen expression. Despite the different biologic values of Ki67 and HLA-DR antigens, we suggest the joint evaluation of both antigens as a useful marker of aggressive behavior in melanoma.
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PMID:Ki67 antigen expression correlates with tumor progression and HLA-DR antigen expression in melanocytic lesions. 169 3

Immunohistochemical characterization is an accepted method of human cell typing and tumor diagnosis. The differentiation of undifferentiated carcinoma from amelanotic melanoma is usually achieved by demonstration of cytokeratin (CK) intermediate filaments in carcinoma but not in melanoma. In examination of 100 melanomas fixed in formalin or methacarn and frozen tissue sections, we have found CK-immunoreactivity in 2, 8, and 21% of cases, respectively, with multiple anticytokeratin antibodies displaying overlapping antigenic specificities. In addition, we have confirmed the anomalous expression of low molecular weight CK proteins by one- and two-dimensional gel electrophoresis and immunoblotting of extracts of an immunohistochemically positive case. This latter finding indicates that CK staining in melanomas reflects the presence of authentic CK peptides and is not an artefact induced by fixation or cross-reacting antibodies. These observations have direct implications for the application of immunohistochemistry to the present practice of diagnostic surgical pathology. The anomalous CK expression by melanoma limits the diagnostic reliability of immunohistochemically demonstrated CK alone to indicate a diagnosis of carcinoma, without the concomitant detection of additional tumor-associated antigens. The finding of anomalous CK expression only in metastatic or recurrent melanomas raises an interesting question of possible association with tumor progression.
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PMID:Anomalous cytokeratin expression in malignant melanoma: one- and two-dimensional western blot analysis and immunohistochemical survey of 100 melanomas. 169 24

Twenty-three patients with malignant melanoma metastatic to the central nervous system (CNS) were treated with intracarotid cisplatin-based chemotherapy. Twenty-two had failed prior cranial radiation therapy (one patient refused radiation therapy) and had progressive brain metastases documented by computerized tomography (CT). Intracarotid cisplatin 40-75 mg/m2 was administered alone (seven patients) with 1,3-bis(2-Chloroethyl)-1-nitrosourea (BCNU) (13 patients) or bleomycin (three patients). Courses were repeated monthly with CT scan. Seven patients (30%) had objective improvement in CT scans and three patients (13%) had stabilization of disease. The median time to tumor progression for responding patients was 20 weeks (range 8-34 weeks) while stable disease ranged from 9-12 weeks. In three patients the extracranial disease progressed while the brain metastases responded. Neurological and retinal toxicity were potential complications of therapy. Intracarotid cisplatin-based chemotherapy may be useful for palliation in selected patients with malignant melanoma and CNS metastases.
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PMID:Intracarotid cisplatin-based chemotherapy in patients with malignant melanoma and central nervous system (CNS) metastases. 169 2

The src-gene family in mammals and birds consists of 9 closely related protein tyrosine kinases. We have cloned the c-yes and fyn homologues of the src-family from the teleost fish Xiphophorus helleri. Both genes show a high degree of sequence conservation and exhibit all structural motifs diagnostic for functional src-like protein tyrosine kinases. Sequence comparisons revealed three domains (exon 2, exons 3-6, exons 7-12) which evolve at different rates. Both genes exhibit an identical expression pattern, with preferential expression in neural tissues. No transcripts of c-yes were found in liver which is contrary to the situation in higher vertebrates. In malignant melanoma, elevated levels of c-yes and fyn were detected indicating a possible function during secondary steps of tumor progression for src-related tyrosine kinases.
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PMID:Conservation of structure and expression of the c-yes and fyn genes in lower vertebrates. 170 52


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