National Cancer Institute®
Last Modified: June 1, 2002
UI - 12003619
AU - Robertson DM; Salomao DR
TI - The effect of transpupillary thermotherapy on the human macula.
SO - Arch Ophthalmol 2002 May;120(5):652-6
AD - Department of Ophthalmology, Mayo Clinic, Rochester, MN 55905, USA. email@example.com
UI - 12003630
AU - Benson WE
TI - The COMS: why was it not stopped sooner?
SO - Arch Ophthalmol 2002 May;120(5):672-3; discussion 673
UI - 11941244
AU - De Potter P
TI - [Choroidal melanoma: current therapeutic approaches]
SO - J Fr Ophtalmol 2002 Feb;25(2):203-11
AD - Unite d'Oncologie Oculaire, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, 10 Avenue Hippocrate, 1200 Bruxelles, Belgique.
The management of posterior uveal melanoma has evolved tremendously over the past decades and more recently there has been a trend toward more focal conservative treatment. Transpupillary thermotherapy (TTT) with infrared diode laser (810nm) is the newest modality used as primary treatment or as a complement to radiotherapy or surgical resection in selected cases of choroidal melanoma. Plaque radiotherapy or charged-particle irradiation is particularly recommended for medium- or small-sized uveal melanoma not suitable to TTT or resection. Special custom-designed plaque radiotherapy (iodine-125) can be used for the iris and ciliary body, or in juxtapaillary choroidal melanoma. The tumor control rate after plaque or charged-particle radiotherapy appears to be similar but charged-particle irradiation may produce worse anterior-segment complications than plaque radiotherapy. Stereotactic radiation therapy for choroidal melanoma may be effective in controlling tumor growth, but the number of patients treated with this approach is too small to draw solid conclusions. Local tumor resection using trans-scleral resection is mainly suitable for selected iris, ciliary body, or anterior choroidal melanoma, particularly with smaller basal dimensions and greater thickness. Endoresection may preserve central vision or temporal field when radiotherapy would be expected to cause optic neuropathy. Longer follow-up is necessary to establish the efficacy of tumor control. Combined therapies (radiotherapy plus TTT or tumor resection plus TTT) appear to be more effective in decreasing the incidence of intraocular tumor recurrence. Enucleation is still performed for large uveal melanoma when there is no hope of regaining useful vision. Based on the published ophthalmology literature, it seems that enucleation carries the same survival prognosis as each of the conservative treatment modalities.
UI - 11941245
AU - Snyers B; De Potter P
TI - [Advantages of digital indocyanine green angiography for diagnosing choroidal tumors]
SO - J Fr Ophtalmol 2002 Feb;25(2):212-20
AD - Unite de Retine Medicale, Bruxelles, Belgique.
Indocyanine green angiography (ICG) is a well-known ancillary test for evaluation of choroidal tumors. The authors review the different images seen in choroidal nevus, melanoma, metastasis, hemangioma, osteoma, and vortex vein varix. ICG appears to be useful for the diagnosis of non pigmented choroidal tumors. In addition, ICG provides good information on the limits of pigmented tumors, particularly for the follow-up of a growing tumor and the choice of treatment.
UI - 11813118
AU - Caminal Mitjana JM; Quintana Casany M; Pera Fabregas J; Cinos Cope C;
TI - Guedea F [Results of Iodine-125 radiotherapy in the treatment of uveal melanoma]
SO - Arch Soc Esp Oftalmol 2002 Jan;77(1):29-38
AD - Ciutat Sanitaria i Universitaria de Bellvitge, L'Hospitalet, Barcelona, Espana.
PURPOSE: To evaluate our experience in the treatment of uveal melanoma by means of Iodine-125 brachytherapy. A reprospective case series study. MATERIAL AND METHOD: Patients diagnosed of uveal melanoma and treated with Iodine-125 brachytherapy in the Ciudad Sanitaria y Universitaria de more than one year. RESULTS: During the period of study, 145 patients were diagnosed of uveal melanoma, of which, 77 were treated with Iodine-125 COMS type plaques; among these, 58 were elegible for this study. After a mean of 2.4 year follow up period (878 days) a mean reduction in height of 53.84% and a mean reduction in volume of 75.88% was observed. As for visual acuity, 32.7% of patients presented a vision of 0.1 or better in last follow up check; 13.5% presented low vision at the moment of diagnosis and continued the same up to last follow up check. The rest of patients experienced loss which conditioned vision to less than 0.1. As for complications, we have observed transient diplopia (8.6%), cataract (3.4%), vitreous bleeding (10.3%), neovascular glaucoma (6.8%), radiation retinopathy (17.24%), radiation neuropathy (6.8%), posterior scleritis (2%), pigmental scattering (2%), tumor progression (2%), endophtalmitis (2). Secondary enucleations were carried out in 6.8% of patients. Metastatic disease was observed in 15.5% of the patients. CONCLUSIONS: Brachytherapy with Iodine-125 may induce significant regression in most of patients affected of uveal melanoma, with good preservation of visual acuity and a low rate of complications.
UI - 11725771
AU - Muscat S; Srinivasan S; Sampat V; Kemp E; Parks S; Keating D
TI - Optical coherence tomography in the diagnosis of subclinical serous detachment of the macula secondary to a choroidal nevus.
SO - Ophthalmic Surg Lasers 2001 Nov-Dec;32(6):474-6
AD - Electrodiagnostic Imaging Unit, Tennent Institute of Ophthalmology Gartnavel General Hospital, Glasgow, Scotland.
We present a case in which optical coherence tomography (OCT) aided in the diagnosis of subretinal fluid (SRF) secondary to a choroidal nevus. A patient with a raised lesion above the left optic disc and distorted central vision was referred to our unit because of suspected choroidal melanoma. Fundus fluorescein angiography and slit-lamp investigation did not indicate any areas of SRF; however, OCT showed serous detachment in the macular area. The lesion was treated with laser photocoagulation and, when reviewed at four weeks post-treatment, repeat OCT scans showed that the area of SRF had cleared. In this case OCT was able to detect a subclinical serous detachment in the macula. This may have important implications in the monitoring of patients with small suspicious lesions.
UI - 12045056
AU - Kaiserman I; Anteby I; Chowers I; Blumenthal EZ; Kliers I; Pe'er J
TI - Changes in ultrasound findings in posterior uveal melanoma after Ruthenium 106 brachytherapy.
SO - Ophthalmology 2002 Jun;109(6):1137-41
AD - Department of Ophthalmology, Hadassah University Hospital, Jerusalem, Israel. Igork@cc.huji.ac.il
PURPOSE: To analyze the postbrachytherapy ultrasonographic dynamics of uveal melanoma tumor height and internal reflectivity. DESIGN: Prospective, comparative, observational case series. PARTICIPANTS: One hundred forty-seven patients (147 eyes) with posterior uveal melanoma having a mean age of 61 years (range, 29-97 years) who were treated with Ruthenium 106 brachytherapy. METHODS: Patients were followed-up with ultrasonography using both A and B modes of standardized echography every 6.7 +/- 0.3 months (mean +/- standard error of the mean) for a total of 1001 ultrasound examinations. On average, each patient was examined 5.8 times (range, 3-17 times). The echographic parameters included tumor base size, height, internal reflectivity, regularity, vascularity, and extra-scleral extension. To compare the response of tumors of different sizes, each tumor was standardized to its initial size at brachytherapy. MAIN OUTCOME MEASURES: The dynamics of the tumor height and internal reflectivity. RESULTS: At the time of brachytherapy, the mean height of the tumors was 5.2 mm (range, 2.2-11.8 mm). After brachytherapy, 142 tumors (96.6%) responded by a decrease in height. The decrease in height was at an initial rate of approximately 3% per month. Most of the tumors did not regress entirely; rather, their height stabilized on a constant value (on average 61% of the initial height) after approximately 18 to 24 months. The decrease in height after brachytherapy was best fitted by the sum of a first order exponential decay and a constant (h = 61 + 35*e(-0.12t), in which t = time in months). The half-life of the decay was 5.8 months. Large tumors (>8 mm) had a faster initial decrease in height, and stabilized on a lower percentage of their initial height (50%) compared with small tumors (70%). Thus, the half-life of the height exponential decay was 5.3 months for small tumors (2-4 mm) and 3.3 months for the large tumors (>8 mm). Internal reflectivity increased from a mean of 40% before therapy to 70% after 2 years. The dynamics of the reflectivity were best fitted with the function: f = 45 + 24(1-e(-0.09t)). Larger tumors, which initially had lower internal reflectivity, presented with a slower increase in internal reflectivity (t() = 8.7 months) compared with smaller tumors (t(1/2) = 5 months). CONCLUSIONS: The postbrachytherapy ultrasonographic dynamics of uveal melanomas resemble a function composed of the sum of a constant and a first order exponent, suggesting the possible existence of two components (cell populations), one unaffected by brachytherapy and the other a radiosensitive population that reacts to brachytherapy in an exponential decay. An exponential decay can imply that the postbrachytherapy death of each tumor cell is a stochastic Markovian process that is independent of the death of other tumor cells.
UI - 12014934
AU - Recsan Z; Karlinger K; Fodor M; Zalatnai A; Papp M; Salacz G
TI - MRI for the evaluation of scleral invasion and extrascleral extension of uveal melanomas.
SO - Clin Radiol 2002 May;57(5):371-6
AD - Second Department of Ophthalmology, Faculty Medicine, Semmelweis University, Budapest, Hungary.
AIM: To study the diagnostic value of MRI for the detection of scleral infiltration and extrascleral extension of uveal melanoma. MATERIALS AND METHODS: Twelve consecutive patients with clinically suspected large uveal melanoma were examined by MRI. All of the patients underwent enucleation or exenteration. The clinical and histopathological findings were compared. RESULTS: The clinical diagnosis of uveal malignant melanoma was confirmed by histology in each case. MRI allowed detection of scleral infiltration with a sensitivity of 100% and a specificity of 50%. For extrascleral extension, MRI had a sensitivity of 100% and specificity of 89%. CONCLUSIONS: Using fat suppression technique and enhancement with contrast medium, MRI proved to be a valuable ancillary method for the assessment of scleral infiltration and extrascleral extension. Copyright 2002 The Royal College of Radiologists.
UI - 11944865
AU - Mueller AJ; Bartsch DU; Schaller U; Freeman WR; Kampik A
TI - Imaging the microcirculation of untreated and treated human choroidal melanomas.
SO - Int Ophthalmol 2001;23(4-6):385-93
AD - Augenklinik der Universitat, Munchen, Germany.
INTRODUCTION: Histologically demonstrable microcirculation patterns (microcirculation pattern) of human choroidal melanomas have prognostic significance for the patient. We report on our experience in imaging these microcirculation pattern in vivo using simultaneous confocal Fluorescein (FA)- and Indocyaninegreen (ICG) angiography before and after brachytherapy. PATIENTS AND METHODS: The simultaneously procured confocal FA- and ICG angiograms of 50 patients with untreated choroidal melanomas were studied for the visibility of microcirculation pattern. Patients were also followed with simultaneous FA/ICG after brachytherapy. RESULTS: Confocal FA disclosed signs of tumor vascularization in 12 (24%) of the 50 examined patients but microcirculation pattern only in 3 patients (6%). In contrast, simultaneously obtained confocal ICG disclosed microcirculation pattern in 47 patients (94%). In 10 (77%) of the 13 patients the tumor microcirculation changed considerably after brachytherapy: Distortion, thickening, thinning, as well as complete obliteration of vessels could be observed. CONCLUSION: Histologically demonstrated microcirculation pattern can be imaged in vivo. This offers the possibility to assess the likely biologic behavior of the individual tumor without the need for obtaining a cytologic or histologic specimen via enucleation or fine-needle biopsy. Confocal ICG angiogiography images microcirculation pattern better than FA which can be explained by the different absorption-, fluorescence- and exudation-characteristics ICG. Follow-up with confocal ICG of choroidal melanomas after brachytherapy shows different features and allows for visualization of the microcirculation reaction to the treatment which might be a useful tool for studying the effects of future anti-angiogenesis based tumor therapies.
UI - 11979433
AU - Papadopoulos S; Benter T; Anastassiou G; Pape M; Gerhard S; Bornfeld N;
TI - Ludwig WD; Dorken B Assessment of genomic instability in breast cancer and uveal melanoma by random amplified polymorphic DNA analysis.
SO - Int J Cancer 2002 May 10;99(2):193-200
AD - Department of Obstetrics and Gynecology, Free University of Berlin, Berlin, Germany.
Some types of cancer have been associated with abnormal DNA fingerprinting. We used random amplified polymorphic DNA (RAPD) to generate fingerprints that detect genomic alterations in human breast cancer. Primers were designed by choosing sequences involved in the development of DNA mutations. Seventeen primers in 44 different combinations were used to screen a total of 6 breast cancer DNA/normal DNA pairs and 6 uveal melanoma DNA/normal DNA pairs. Forty-five percent of these combinations reliably detected quantitative differences in the breast cancer pairs, while only 18% of these combinations detected differences in the uveal melanoma pairs. Fourteen (32%) and 12 (27%) primers generated a smear or did not produce any band patterns in the first and second cases, respectively. Taking into account the ability of RAPD to screen the whole genome, our results suggest that the genomic damage in breast cancer is significantly higher than in uveal melanoma. Our study confirms other reports that the molecular karyotypes produced with random priming, called amplotypes, are very useful for assessing genomic damage in cancer. Copyright 2002 Wiley-Liss, Inc.
UI - 11992876
AU - Seifert P; Spitznas M
TI - Axons in human choroidal melanoma suggest the participation of nerves in the control of these tumors.
SO - Am J Ophthalmol 2002 May;133(5):711-3
AD - Alfried-Krupp Laboratory, Department of Ophthalmology, University of Bonn, Germany. firstname.lastname@example.org
PURPOSE: To furnish morphologic evidence of autonomic nervous system influence on choroidal melanoma. DESIGN: Histopatholgic case report. METHODS: In the enucleated eye of a 72-year-old woman, portions of a mixed-cell choroidal melanoma were processed for electron microscopy, and ultrathin sections were screened painstakingly under magnifications of x13,000 and x23,000. RESULTS: The connective tissue of the melanoma contained macrophages, blood vessels, and profiles of several nonmyelinated nerve fiber bundles with a maximum of 6 axons. CONCLUSION: The existence of axons in neoplastic tissue indicates nervous input and/or output. This led us to conclude that the reaction of the melanoma is subjected to vegetative influences, yet to an unknown extent.
UI - 11941255
AU - Lumbroso L; Levy C; Plancher C; Frau E; D'hermies F; Schlienger P;
TI - Dendale R; Mammar H; Delacroix S; Nauraye C; Noel G; Ferrand R; Desblancs C; Mazal A; Validire P; Asselain B; Desjardins L [Results of proton beam irradiation for treatment of choroidal melanoma]
SO - J Fr Ophtalmol 2002 Mar;25(3):290-7
AD - Service d'Ophtalmologie, Institut Curie, 26 rue d'Ulm, 75231, Paris Cedex 05.
PURPOSE: To evaluate the results of proton beam irradiation of choroidal melanomas on a large series of patients. PATIENTS AND METHODS: Retrospective analysis of a series of patients treated with proton beam evaluate the local tumor control as well as the general progression and metastatic rate of the patients. Statistical analysis served to isolate risk factors for relapse or metastasis. RESULTS: We treated 1062 patients during the study period, with a median follow-up of 38 months. Local control was obtained for 97.1% of the patients. Tumors anterior to the equator were at risk for relapse. The survival rate was 92% at 2 years and 78% at 5 years. 73.1% of the 1062 patients died from metastasis, 6.1% of living patients presented with metastatic disease. The risk factors for death were the initial diameter, the age of the patient, and large tumor volume at diagnosis. Metastasis were essentially hepatic (94.6%). Risk factors for metastasis were: a large tumor volume, a lesion anterior or straddling the equator and the age of the patient. Ocular complications may induce a visual loss of 0.1 and less in 47% of the patients, due to optic nerve head and macular ischemia. 6% of the patients required secondary enucleation due to local complications (neovascular glaucoma). CONCLUSION: Proton beam irradiation of choroidal melanoma allows good tumor control and eye retention. The survival prognosis is associated with the initial volume of the tumor. The functional results may be improved and new therapeutics are needed to treat metastatic disease.
UI - 12058487
AU - Straatsma BR
TI - The Jules Francois Memorial lecture. The collaborative ocular melanoma study and management of choroidal melanoma.
SO - Bull Soc Belge Ophtalmol 2002;(283):5-11
AD - Jules Stein Eye Institute, Department of Ophthalmology, UCLA School of Medicine, University of California, Los Angeles, California, USA.
UI - 12036969
AU - Woodward JK; Nichols CE; Rennie IG; Parsons MA; Murray AK; Sisley K
TI - An in vitro assay to assess uveal melanoma invasion across endothelial and basement membrane barriers.
SO - Invest Ophthalmol Vis Sci 2002 Jun;43(6):1708-14
AD - Academic Unit of Ophthalmology and Orthoptics, Royal Hallamshire Hospital, University of Sheffield, Sheffield, United Kingdom. email@example.com
PURPOSE: To develop a modified in vitro invasion assay to assess uveal melanoma invasion across endothelial and basement membrane barriers. METHODS: Using permeable cell culture supports, endothelial cells were grown to confluence on an 8-microM pore polycarbonate membrane precoated with an artificial basement membrane. Primary uveal melanomas were grown as short-term cultures at 37 degrees C and 5% CO2 and invaded through the endothelial cell layer and basement membrane. Invading cells were counted under x400 magnification on the lower surface of the membrane. Levels of invasion were correlated with histopathologic markers of prognosis. The relative invasion of individual tumors was established by comparison of invasion through both endothelial and basement membrane barriers with invasion through basement membrane components alone. RESULTS: A series of 13 primary tumors were studied using the modified invasion assay. Tumors varied in their propensity to permeate both barriers. In all cases the endothelial cell layer reduced invasion, but the effect varied between tumors. CONCLUSIONS: Some tumors were more adept at overcoming the additional endothelial cell layer, whereas invasion of others was severely inhibited. Tumor invasion through the transendothelial model was found to correlate more closely with clinical characteristics associated with invasion, than was invasion through basement membrane components alone. The transendothelial model may represent a more realistic model for the in vitro study of invasion of uveal melanoma cells, providing a useful in vitro system for the investigation of cellular interactions during the invasion process.
UI - 12036989
AU - Levi-Schaffer F; Micera A; Zamir E; Mechoulam H; Puxeddu I; Piliponsky
TI - AM; Aloe L; Pe'er J Nerve growth factor and eosinophils in inflamed juvenile conjunctival nevus.
SO - Invest Ophthalmol Vis Sci 2002 Jun;43(6):1850-6
AD - Department of Pharmacology and the David R. Bloom Center for Pharmacy School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. firstname.lastname@example.org
PURPOSE: To study both systemic and ocular nerve growth factor (NGF) in inflamed juvenile conjunctival nevus (IJCN), a benign, inflammatory juxtalimbal lesion characterized by many intralesional eosinophils, and to investigate the behavior of eosinophils cocultured on lesional and extralesional fibroblasts obtained from IJCN biopsies, in relation to NGF. METHODS: Eight patients with IJCN (7-15 years old) and six with noninflamed conjunctival compound nevus (12-30 years old) participated in the study. Conjunctival biopsy specimens were used for routine histology, immunohistochemistry (NGF, trkA, eosinophil cationic protein, and tryptase determination), in situ hybridization (NGF mRNA), and determination of fibroblast growth. Blood of patients with IJCN was used to measure NGF levels (by ELISA) and to isolate eosinophils (magnet activated cell sorter [MACS]). Eosinophils were seeded on lesional and extralesional fibroblasts and their adherence, survival (by trypan blue staining), and functional activity (by eosinophil peroxidase [EPO] assay) were assessed after 4 days. RESULTS: NGF in the blood of patients with IJCN and eosinophils and mast cells in their conjunctivas, were significantly elevated. NGF protein, NGF mRNA, and trkA were found to be increased in IJCN biopsy specimens compared with noninflamed compound nevi. Some NGF and trkA colocalized with eosinophils and mast cells. Lesional fibroblasts produced high amounts of NGF in comparison with extralesional fibroblasts and significantly enhanced eosinophil adherence, without influencing either their viability or activation. Adherence and EPO release were increased, in both lesional and extralesional fibroblasts. CONCLUSIONS: The triggering factors that lead to the prominent inflammation in IJCN are unknown. The data in the current study, showing the presence of increased NG-trkA, eosinophils, and mast cells in IJCN and the modulation of eosinophil properties by lesional fibroblasts partly through NGF, suggest a possible association between IJCN and allergic inflammation. Alternatively, this process may represent a direct immune response induced by the nevus itself.
UI - 11955309
AU - Gao Y; Dai H; Chen T; Liu Y; Xiao S; Liu M; Li G
TI - [Treatment of choroidal melanoma with X-ray knife]
SO - Chung Hua Yen Ko Tsa Chih 2002 Feb;38(2):94-7
AD - Department of Ophthalmology, Beijing Hospital, Beijing 100730, China. email@example.com
OBJECTIVE: To detect and analyze the therapeutic effects of X-ray knife for treatment of choroidal melanoma with the fixation of the eyeball. METHODS: The average size of the tumors in 16 eyes of 16 cases was 11.8 mm x 10.0 mm x 4.5 mm. The eyeballs were fixed with four rectus retractable sutures under local anesthesia (no use of retrobulbar injection). The superior and inferior rectus sutures penetrated the upper and lower lids at the middle part of fornixes, and the four sutures were anchored at the positions: above the eyebrow, inferior orbital rim, root of nose and lateral orbital rim respectively and deep to the fascia. A stereotactic linear accelerator, Vrianc 2100 C, was used for the radiosurgery, with an average marginal dose 23.4 Gy. The mean follow-up time was 18.5 months. RESULTS: The tumors in 7 cases (43.8%) shrinked notably during 6 - 12 months after therapy. In the postoperative 1 - 2 years, the tumors in 11 eyes (68.8%) were decreased in size, among them, in 4 eyes only a flat scar remained and in 3 eyes the shrinkage was not significant. Enucleation was performed in 3 patients because of a little increase in size. The total local control rate was 81.3%. There were no marked side effects except small hemorrhages in or under the retina. Fixations of all eyeballs were very stable, and the orientation of radiotherapy was accurate. CONCLUSIONS: The therapeutic effects of choroidal melanoma with X-ray knife are quite good, and no significant complications are found. There is a higher rate of local control. The fixation of eyeball with four rectus sutures penetrating eyelids is very stable and reliable.
UI - 12040282
AU - Werschnik C; Lommatzsch PK
TI - Long-term follow-up of patients with conjunctival melanoma.
SO - Am J Clin Oncol 2002 Jun;25(3):248-55
AD - Klinik und Poliklinik fur Augenheilkunde der Martin-Luther-Universitat Halle-Wittenberg, Germany.
Data from long-term follow-up examinations of patients with conjunctival melanoma are limited. A retrospective study of survival rates and local tumor relapse rates was performed on 85 patients initially treated between 1958 and 1993. Therapeutic procedures were local excision, local excision followed by brachytherapy, local excision combined with cryotherapy, and local excision followed by either irradiation or cryotherapy and adjuvant mitomycin C (MMC) application. The Kaplan-Meier method was used to estimate cumulative survival rates and event rate curves. Clinical parameters of the patients and the tumors were obtained and analyzed for their relation to tumor recurrence and death from metastatic melanoma using the multivariate Cox hazards modeling. The median follow-up duration among the surviving patients was 13.1 years (mean 13.8 years). The cumulative 10-year survival rate of the 85 patients based on all causes of death was 62.5%, and that based on tumor-related death was 77.7%. Patient age greater than 55 years, higher TNM category, and unfavorable tumor location (palpebral conjunctiva, fornix, caruncle, corneal stroma, eyelid) were identified as prognostic factors for death from metastatic melanoma. Tumors with unfavorable location, higher TNM grade, and excision alone as initial therapy showed a higher cumulative probability of local relapse than favorably located (bulbar and limbal conjunctiva) tumors, lower TNM grade, and excision plus adjuvant therapy. The behavior of conjunctival melanomas remains unpredictable in individual cases. To minimize local recurrence rate surgical excision should be combined with an adjunctive procedure such as irradiation, cryotherapy, or local chemotherapy with MMC. Randomized prospective multicentric studies are required.
UI - 12067204
AU - Seftor EA; Meltzer PS; Kirschmann DA; Pe'er J; Maniotis AJ; Trent JM;
TI - Folberg R; Hendrix MJ Molecular determinants of human uveal melanoma invasion and metastasis.
SO - Clin Exp Metastasis 2002;19(3):233-46
AD - Department of Anatomy and Cell Biology, College of Medicine and The Holden Comprehensive Cancer Center, University of Iowa, Iowa City 52242-1109, USA.
The molecular analysis of cancer has benefited tremendously from the sequencing of the human genome integrated with the science of bioinformatics. Microarray analysis technology has the potential to classify tumors based on the differential expression of genes. In the current study, a collaborative, multidisciplinary approach was utilized to study the molecular determinants of human uveal melanoma invasion and metastasis. Uveal melanoma is considered the most common primary intraocular cancer in adults, resulting in the death of approximately 50% of patients affected. Unfortunately, at the time of diagnosis, many patients already harbor microscopic metastases, thus underscoring a critical need to identify prognostic markers indicative of metastatic potential. The investigative strategy consisted of isolating highly invasive vs. poorly invasive uveal melanoma cells from a heterogeneous tumor derived from cells that had metastasized from the eye to the liver. The heterogeneous tissue explant MUM-2 led to the derivation of two clonal cell lines: MUM-2B and MUM-2C. Further morphological and functional analyses revealed that the MUM-2B cells were epithelioid, interconverted (expressing mesenchymal and epithelial phenotypes) highly invasive, and demonstrated vasculogenic mimicry. The MUM-2C cells were spindle-like, expressed only a vimentin mesenchymal phenotype, poorly invasive, and were incapable of vasculogenic mimicry. The molecular analysis of the MUM-2B vs. the MUM-2C clones resulted in the differential expression of 210 known genes. Overall, the molecular signature of the MUM-2B cells resembled that of multiple phenotypes--similar to a pluripotent, embryonic-like genotype. Validation of select genes that were upregulated and down-regulated was conducted by semiquantitative RT-PCR measurement. This study provides a molecular profile that will hopefully lead to the development of new molecular targets for therapeutic intervention and possible diagnostic markers to predict the clinical outcome of patients with uveal melanoma.
UI - 11901310
AU - Ellerhorst JA; Bedikian AY; Smith TM; Papadopoulos NE; Plager C; Eton O
TI - Phase II trial of 9-nitrocamptothecin (RFS 2000) for patients with metastatic cutaneous or uveal melanoma.
SO - Anticancer Drugs 2002 Feb;13(2):169-72
AD - Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030-4095, USA. firstname.lastname@example.org
The camptothecin derivative 9-nitrocamptothecin (9-NC) has demonstrated clinical activity in patients with ovarian and pancreatic carcinomas. Preclinical studies have shown promising activity of 9-NC for melanoma. We have thus conducted a phase II clinical trial of 9-NC for patients with metastatic cutaneous and uveal melanoma. Twenty-eight patients were enrolled in the trial, with diagnoses evenly divided between the two types of melanoma. 9-NC was administered orally at a starting dose of 1.5 mg/m(2)/day for 5 consecutive days of each week. No complete or partial responses were observed. Stabilization of disease was achieved in four individuals (15%) for durations of 3, 4, 6 and 8 months. Hematologic toxicity was moderate. Gastrointestinal side effects were common with 43% of the patients experiencing grade 3 or 4 diarrhea and 18% reporting grade 3 or 4 vomiting. In contrast to other 9-NC clinical trials, no patients developed chemical cystitis with gross hematuria. We conclude that, in keeping with the general chemoresistance of melanoma, 9-NC at the dose and schedule studied in this trial is significantly toxic and is not active for metastatic melanoma of cutaneous or uveal origin.
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