Prognosis of Malignant Melanomas of the Choroid and Ciliary Body

Paul, Eleanor V.; Parnell, Benjamin L.; Fraker, May

doi:10.1097/00004397-196206000-00007

Cited by 182 publications

(68 citation statements)

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“…In the current study, four out of six tumours were composed predominantly of epithelioid cells (which have the worst clinical prognosis; Paul et al, 1962). Unfortunately, given the small number of tumours used and the predominance of epithelioid morphology of tumours in the current study, we are unable to comment on any possible relationship between tumour morphology in vitro and invasive properties in vivo.…”

Section: Discussionmentioning

confidence: 56%

Tamoxifen, 17β-oestradiol and the calmodulin antagonist J8 inhibit human melanoma cell invasion through fibronectin

Dewhurst

Gee²,

Rennie³

et al. 1997

Br J Cancer

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Summary Invasion through stromal extracellular matrix (ECM) is part of the complex, multistep process of tumour cell invasion and metastasis. Our group has previously demonstrated that calcium and calmodulin are important in another step in the metastatic cascadethat of attachment of cells to ECM. Interestingly, the non-steroidal anti-oestrogen tamoxifen (which also has calmodulin antagonist activity), used in the treatment of breast cancer and now in metastatic cutaneous melanoma, can inhibit the attachment of normal and neoplastic cells to ECM. In this study, we investigated whether such drugs, known to inhibit cell attachment, could also subsequently reduce their invasion through a layer of human fibronectin. We examined the ability of the specific calmodulin antagonist J8, tamoxifen and its two major metabolites, N-desmethyltamoxifen (N-des) and 4-hydroxytamoxifen (4-OH), as well as the pure anti-oestrogen ICI 182,780 and 17,Boestradiol to inhibit invasion of the human cutaneous melanoma cell line, A375-SM, uveal melanoma cells and uveal melanocytes. A375-SM cells and uveal melanoma cells showed a high level of invasion (15.2% and 33.7% respectively) compared with melanocytes (around 5%) under the experimental conditions used. Submicromolar concentrations of N-des, tamoxifen, J8 and 1 7,B-oestradiol significantly reduced the invasiveness of the A375-SM cell line. The uveal melanoma cells also showed similar inhibition, although at higher concentrations of these agents. 4-OH and ICI 182, 780 had little or no effect on invasion of A375-SM cells (these were not tested on uveal melanoma cells). All cells used in this study were found to be negative for type nuclear oestrogen receptors, reinforcing the possibility that tamoxifen and 17,-oestradiol can act via mechanisms unrelated to binding to classical oestrogen receptors to inhibit tumour cell invasion.Keywords: melanoma; invasion; calmodulin antagonists; tamoxifen; oestrogen The prognosis for patients with either cutaneous (Garbe et al, 1995) or uveal melanoma (Bedikian et al, 1981;Rajpal et al, 1983) is poor once these tumours have metastasized. Metastatic spread involves several different stages and, in escaping from the primary tumour and in forming distal metastatic deposits, neoplastic cells need to attach to and subsequently invade through stromal ECM (Albini and Colacci, 1993 for review). Metastatic melanoma cells express a greater range of adhesion molecules than their non-transformed precursor, the melanocyte (Mortarini and Anichini, 1993). Initial attachment of cells to ECM proteins then leads to a reorganization of the cell cytoskeleton to form focal adhesions (Van Leeuwen et al, 1994).In recent years, our laboratory has investigated the role of signal transduction systems in the early stages of cell attachment and shown that attachment of melanoma cells to ECM proteins appears to involve intracellular signalling systems, in particular calcium and calmodulin (MacNeil et al, 1992. We also demonstrated that tamoxifen and two of its major metabolites c...

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Section: Discussionmentioning

confidence: 56%

Tamoxifen, 17β-oestradiol and the calmodulin antagonist J8 inhibit human melanoma cell invasion through fibronectin

Dewhurst

Gee²,

Rennie³

et al. 1997

Br J Cancer

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“…Paul и соавт. [5], проведенном в Институте патологии Вооруженных Сил США (Armed Forses Institute of Pathology, USA) из 3628 пациентов с меланомой выявлены 4 в возрасте до 10 лет с меланомой хориоидеи и цилиарного тела. J. Verdaguer [6] сообщил о 4 из 7 пациентов до 20-летнего возраста с меланомой хориоидеи, первым проявлением заболевания у которых был меланоз склеры.…”

Section: актуальностьunclassified

Melanoma in Сhildren

Makhmudova¹,

Khaitalieva²,

Умарова³

et al. 2015

ONKO

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“…They bear a direct relationship to the prognosis. 21 An accurate classification is also ex tremely valuable for cancers of thyroid, salivary gland and testicle, because in all three instances it gives a fair indication of the prognosis and can influence the choice of therapy.…”

Section: Classification Of Tumorsmentioning

confidence: 99%