DNA Cell Cycle Studies In Uveal Melanoma

Char, Devron H.; Huhta, Kim; Waldman, Frederic M.

doi:10.1016/0002-9394(89)90817-9

Cited by 31 publications

(10 citation statements)

References 91 publications

(43 reference statements)

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“…This observation is consistent with previous results where the doubling time was found to be between 3 and 8 days [Wilson, 2000]. It is well known that UM is characterized by a low number of mitotic figures [Wilson, 2000] and that only 1-8% of tumor cells are BrdU positive [Char et al, 1989]. It is necessary to bear in mind that this tumor is slow growing compared to other neoplasias.…”

Section: Discussion Um Primary Cell Cultures and Cell Cyclesupporting

confidence: 92%

Abnormal cell cycle regulation in primary human uveal melanoma cultures

Pardo

Piñeiro

Fuente

et al. 2004

J of Cellular Biochemistry

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Uveal malignant melanoma is the most frequent primary intraocular tumor in adult humans. The cellular events leading to neoplasic transformation of normal uveal melanocytes are not well known when compared to other cancers. In this study, we investigated the role of G1 and G1/S regulatory proteins of the cell cycle in human uveal melanoma (UM) primary cell cultures, since these proteins are common targets in tumor development. Further, freshly established and characterized tumor cells are a better model for in vitro studies when compared to cell lines established long ago. Human primary cell cultures from eight different UM were established, as well as one primary culture from rhesus uveal normal melanocytes (UNM). Primary human UM cultures were characterized by a low establishment and growing rate. From four successful cultures, three showed a high expression of cyclin D1, cyclin E, p16NK4A, and p27KIP1 with no variations in cyclin A, cyclin-dependent kinase 2 (CDK2), and CDK4. Interestingly, in one of the cultured tumors, tumor suppressor protein retinoblastoma (Rb) did not bind E2F despite the fact that Rb was found in its hypophosphorylated form. No mutations in either RB1 or the Rb-binding pocket of E2F-1 were detected. Furthermore, we identified seven proteins co-immunoprecipitating with Rb in this tumor, including Lamin A/C and six proteins not previously reported to bind Rb: Hsc70, high mobility group protein 1 (HMG-1), hnRPN, glyceraldehyde 3 phosphate dehydrogenase (G3PDH), EF-1, and EF-2. Our results indicate that the overexpression of cyclins D1/E and CDKIs p16 and p27, together with a deregulation of the Rb/E2F pathway, may be implicated in the development of human UM.

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Section: Discussion Um Primary Cell Cultures and Cell Cyclesupporting

confidence: 92%

Abnormal cell cycle regulation in primary human uveal melanoma cultures

Pardo

Piñeiro

Fuente

et al. 2004

J of Cellular Biochemistry

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“…Studies on pre-operatively irradiated human melanoma cells in tissue culture substantiate that irradiation indeed decreases the attachment, growth and viability of melanoma cells in these cultures, while microscopic examination indicated a reduced mitotic activity [7,16,37,63]. No beneficial effect of pre-enucleation irradiation could, however, be observed in terms of better survival after pre-enucleation irradiation as compared with control groups [9,15,40].…”

Section: Histopathology Of Irradiated Melanomasmentioning

confidence: 99%

Uveal melanoma: therapeutic consequences of doubling times and irradiation results; a review

Manschot

Strik

1992

Int Ophthalmol

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Thirty-six of 39 published calculated doubling times (Td's) of uveal melanomas appeared to be longer than 60 days. Metastatic death occurs 35-40 Td's after dissemination. The shortest interval between dissemination and metastatic death in individual patients may, therefore, be calculated as 35 x 60days = 6 years; the interval may extend to 80 years. This suggests, that local therapy cannot influence the survival data within the first 7 post-therapeutic years, because almost all metastatic deaths within these 7 years are due to pretreatment dissemination. For that reason, the published comparative survival analyses after various therapies have within this period failed to show statistically significant death rates differences.Microscopically viable melanoma tissue has been noted in 215 of 231 histopathologically studied irradiated uveal melanomas. Observed mitotic figures 4-6 years after irradiation indicate retained reproductive integrity. This constitutes a -by enucleation avoidable -incremental risk for post-irradiation exponential growth and dissemination. The risk cannot become statistically manifest before a -> 10-year follow-up period. Retained, generally poor, visual acuity in a small percentage of patients cannot balance the incremental risk/benefit ratio of irradiation. A few, at present justifiable, indications for radiotherapy on uveal melanomas are enumerated.

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“…These radioresistant cells were able to divide, probably due to the favourable conditions of the culture medium, whereas inside the necrotic tumour mass living cells may have been blocked in quiescence. Living cultured tumour cells treated by brachytherapy have already been reported (Char et al 1989), although this is, to our knowledge, the first observation noted after proton beam therapy. In addition, the 36‐month survival period after initial therapy is longer than the survival periods reported after brachytherapy.…”

mentioning

confidence: 65%