Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of the marine furanoditerpenes, spongiatriol (SP) and episopongiatriol (ESP), were compared in two sublines of human melanoma cells (MM96E and MM96L) derived from the same metastatic lesion. MM96E had higher tyrosinase activity and lower expression of alkaline phosphatase but was otherwise indistinguishable from MM96L. SP and ESP treatment of both cell lines for 72 h at cytostatic doses inhibited B8G3 expression and tyrosinase activity but had little effect on the expression of tyrosinase antigen. MM96L cells were affected more than MM96E. SP and ESP induced apoptosis in both cell lines, ESP causing dendritic morphology in a proportion of MM96L cells. SP induced a marked G2/M arrest in MM96E cells. SP and ESP together define subtle qualitative and quantitative differences in human melanoma phenoypes, possibly based on expression of a repertoire of neurotransmitter receptors.
Melanoma Res
PMID:Isomers of a marine diterpene distinguish sublines of human melanoma cells on the basis of apoptosis, cell cycle arrest and differentiation markers. 142 91

The ability of melanoma cells to metastasize is largely dependent upon cell surface molecules that mediate cell-matrix and cell-cell interactions. Our aim was to investigate the expression of such molecules (adhesion molecules) on tissue sections of a series of melanocytic lesions in different stages of tumour progression. Four common naevi, four congenital naevi, four dysplastic naevi, three Spitz naevi, 20 primary melanomas and 15 metastatic melanomas were tested with an alkaline phosphatase/anti-alkaline phosphatase technique and a panel of monoclonal antibodies directed toward different alpha subunits of VLA receptors, beta 1, VNR-alpha and beta 3 subunit, and CD44 hyaluronate receptor. Only metastatic melanomas expressed the alpha 4 subunit, and only thick primary melanomas and metastases expressed the beta 3 subunit. The alpha 6/beta 1 chain was expressed at significantly higher levels on benign lesions, and a trend towards increased expression of alpha 2 and alpha 3 subunits was found in malignant versus benign lesions. Our results show that the pattern of integrin expression changes in melanocytic lesions along with malignant transformation.
Melanoma Res 1993 Aug
PMID:Adhesion molecule profile and malignancy of melanocytic lesions. 821 55

Sixty-five patients with advanced melanoma treated in phase II trials with interferon-alpha and high dose interleukin-2 were analysed for pretreatment prognostic parameters. Three levels of response were used: objective remission [three complete response (CR)/14 partial response (PR)], stable disease and progression. Elevated lactate dehydrogenase (LDH), impaired performance status and high tumor load were associated with poor response. Multivariate analysis considering two levels of response [CR/PR vs stable disease (SD)/progressive disease (PD)] did not reveal any model with more than one significant factor. Considering survival, LDH was also a strong factor. Additional prognostic factors here were performance status, metastatic sites, alkaline phosphatase and tumor load. A Cox regression analysis revealed LDH, performance status and metastatic sites as independent factors. The prognostic values of these parameters will have to be confirmed in a larger patient cohort. Using the landmark method, it was estimated whether the response obtained after two cycles of treatment predicted survival. Patients with PD at this time had a median further survival of 6 months, SD of 27 months, and PR/CR of more than 31 months. This observation may help making decisions at this time.
Melanoma Res 1996 Apr
PMID:Prognostic factors for response and survival in patients with metastatic melanoma receiving immunotherapy. 879 Dec 76

Monoclonal antibody (MAb) A103 specifically detects Melan A/MART-1 protein expression. Melan A/MART-1-derived peptides are recognized by CD8+ T-cells and are used in immunotherapy. We examined formalin-fixed paraffin-embedded tissue from 57 melanomas (34 primary, 23 metastatic) and 39 control cases (junctional, dermal, compound, Spitz, Reed and balloon-cell naevi) using the alkaline phosphatase and anti-alkaline phosphatase immunochemical method after antigen retrieval. Immunoreactivity was rated as low, medium or high, and staining pattern as homogeneous or heterogeneous. Staining with MAb A103 showed a sensitivity of 88% for melanoma, with a very high specificity for melanocytic cells. Immunopositivity decreased along with clinical stage, with stage I showing 100%, stage II 88%, stage III 90% and stage IV 75% immunoreactivity. Staining changed from an exclusively homogeneous pattern in the early clinical stages to a more heterogeneous pattern in the later stages. Melanocytic control tissues consisting of naevi of different subtypes all showed weak to moderate homogeneous immunoreactivity, with polarity towards the epidermis. Analysis of short-term melanoma cell cultures using reverse transcription-polymerase chain reaction (RT-PCR) enzyme-linked immunosorbent assay (ELISA) demonstrated mRNA expression in only one third of the originally immunopositive tumours, suggesting rapid mRNA expression loss in culture. MAb A103 allows the detection of melanoma-associated Melan A/MART-1 protein expression in routine archival tissue and thus enables the profiling of melanomas suited for immunotherapy approaches involving Melan A/MART-1 derived epitopes.
Melanoma Res 1998 Aug
PMID:Melan A/MART-1 immunoreactivity in formalin-fixed paraffin-embedded primary and metastatic melanoma: frequency and distribution. 976 9

In this study we evaluated the overexpression status of HER-2 and its prognostic significance on survival in patients with thick cutaneous malignant melanoma. The immuno-alkaline phosphatase antigen detection technique was applied to archival diagnostic material from 51 patients with primary lesions measuring >or= 10 mm in Breslow thickness. Eleven additional patients with primary lesions measuring <or= 1 mm were also studied. HER-2 overexpression was evaluated using conventional light microscopy and an automated cellular imaging system (Chromavision Medical System). Fifteen (29.4%) out of 51 patients with thick lesions showed HER-2 overexpression. In contrast, no overexpression was seen in any of the thin lesions. Overexpression of HER-2 in this group of patients was of no prognostic significance for freedom from recurrence or survival when studied using univariate and multivariate analyses. Whilst the incidence of HER-2 overexpression in patients with thick cutaneous primary melanoma is similar to that reported in breast cancer, it was of no prognostic significance for survival in this study. However, further evaluation in larger numbers of patients with the full spectrum of Breslow thickness is clearly indicated.
Melanoma Res 2002 Apr
PMID:Overexpression of HER-2 in thick melanoma. 1193 Jan 10

Cutaneous melanoma is an extremely heterogenous human cancer. The most aggressive melanoma may contain deregulated cells with undifferentiated/stem cell-like phenotype. A critical mechanism by which melanoma cells enhance their invasive capacity is the dissolution of the intercellular adhesion and the acquisition of mesenchymal features as a part of an epithelial-to-mesenchymal transition. The aim of this study was to clarify the role of a stem cell-like population in human melanomas by means of melanocytic cell culture analysis obtained from distinct histotypes of primary and metastatic malignant melanoma. Patients with advanced melanoma >2 cm in diameter and/or >300 mm surface were enrolled. The melanoma cells were isolated from skin biopsies of lentigo maligna melanoma, superficial spreading melanoma, nodular melanoma, and metastatic melanoma. The colony forming unit assay and alkaline phosphatase stain were evaluated. Cells were subsequently cultured and maintained in different media to evaluate their ability to differentiate into osteogenic and adipogenic lineages. Immunohistochemistry and flow cytometry analysis were performed to evaluate antigenic markers CD90, CD73, CD105, CD146, CD20, CD166, and Nestin. This study confirms that melanoma can include heterogenous cell populations with the ability both to self-renew and to a give rise to differentiated progeny. Melanoma cells displayed intratumoral heterogeneity and dynamic antigen phenotypes. Histologically, transitions from normal skin to melanoma were associated with a gradual increase in the expression of CD146, CD20, CD133, Nestin, and CD73. These molecular profiles could be further analyzed and, in the future, used for the development of novel biomolecular targeted-therapy approaches.
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PMID:Stem cell properties in cell cultures from different stage of melanoma progression. 2370 51

Metastatic uveal melanoma (MUM) has a poor prognosis, with no established standard of care. Delineation of prognostic factors in MUM patients may enable stratified treatment algorithms of stage-specific survival. Overall, 132 MUM patients who presented to a single tertiary institution in Toronto, Canada, over 12 years were identified and data (demographics, clinical status, radiographic images, and laboratory values) were extracted. Associations with systemic first-line treatment outcome 12 weeks after first-line treatment, time to progression (TTP), and overall survival (OS) were explored by univariate and multivariable analysis. Age, presence of liver metastases, and time from primary presentation to metastatic presentation were significant variables affecting first-line treatment outcomes. Age, Eastern Cooperative Oncology Group (ECOG) score, presence of liver metastases, liver metastasis size, neutrophil lymphocyte ratio, absolute neutrophil count, lactate dehydrogenase (LDH), alkaline phosphatase, time from primary presentation to metastatic presentation, and patients receiving surgery as the first-line treatment were significant variables affecting TTP. Age, ECOG score, presence of liver metastases, liver metastasis size, neutrophil lymphocyte ratio, absolute neutrophil count, LDH, and alkaline phosphatase were significant variables affecting OS. Patients who underwent surgery, chemotherapy, immunotherapy, liver-directed therapy, or targeted therapy had better OS compared with patients not receiving treatment with surgery, associated with a significantly better OS compared with all other therapies. Multivariable analysis showed increased age, absence of liver metastases, and absence of bone metastases to be associated with positive treatment outcomes. ECOG score of at least 1, increased LDH, and decreased time from primary to metastatic presentation would predict decreased TTP. Increased LDH, older age, and ECOG score of at least 1 were associated with decreased OS. These results identified prognostic markers and models thereof of treatment benefit and survival. Further validation in larger cohorts is required.
Melanoma Res 2018 12
PMID:Prognostic factors for first-line therapy and overall survival of metastatic uveal melanoma: The Princess Margaret Cancer Centre experience. 3006 47