PURPOSE:To evaluate the value of the apoptosis-suppressing oncogene bcl-2 protein expression in the development and progression of uveal and conjunctival melanomas. METHODS:Using flow cytometry and immunofluorescence methods to detect the bcl-2 protein expression in 40 cases of uveal malignant melanomas (UMM), 5 cases of conjunctival nevi (CN) and 7 cases of conjunctival malignant melanomas (CMM). RESULTS :The expression content of bcl-2 protein in CMM was significantly higher than that in CN (P＜0.05);the bcl-2 protein positive expression percentages in CMM and UMM were 85.71% and 72.50% respectively. The expression content of bcl-2 protein in UMM was not related to pathological classfication, scleral invasion,ciliary body involvement,and tumor dimensions (P＞0.05). CONCLUSIONS: The over-expression of bcl-2 protein and apoptosis suppressing might be related to the pathogenesis of CMM and UMM;bcl-2 protein expression might be helpful in discriminating CN from CMM, but unavailable in evaluating the patholgical malignancy of UMM. （Chin J Ocul Fundus Dis,1997,13: 73-74 ）
Objetive To observe the incidence of extraocular extension of malignant uveal melanoma, the relationship between the incidence and histopathologic type, the characters of clinical manifestation and iconography, and the factors influencing prognosis. Methods Nine cases of extraocular extension of malignant uveal melanoma within last 20 years were analyzed retrospectively. All cases were diagnosed by histopathological examination and most of them had undergone ultrasound and CT examinations. Results The incidence of extraocular extension of malignant uveal melanoma was 15%. Tumors of 6 patients were flat and 2 nodular in shape, 4 epithelial cell and 1 spindle cell in type. The follow-up results of 5 patients in this series indicated that the prognosis was related to the size of the tumor, the degree of extraocular extension, and histopathologic type. Conclusion Extraocular extension of malignant uveal melanoma might happen in early case and the occurrence is usually related to the histopathologic type of the tumor. Iconographic examination is very helpful for diagnosis in extraocular extension of this tfumor. (Chin J Ocul Fundus Dis,1999,15:30-32)
Objective To investigate the expression of pigment epitheliumderived factor (PEDF) and vascular endothelial growth factor (VEGF) in choroidal melanoma. Methods The expression of VEGF and PEDF protein in fifty-eight cases of paraffinembeded choroidal melanoma samples was measured by immunohistochemistry, the expression of PEDF mRNA in thirtynine choroidal melanoma samples was assayed by in situ hybridization. Results PEDF protein was detected in 13/58 cases (22.4%) of choroidal melanoma, the positive rate in nonsclerainvasion group (12/38, 31.6%) was higher (Plt;0.05) than that in sclerainvasion group (1/20, 5%). VEGF protein was detected in 43/58 cases (64%) of choroidal melanoma, the positive rate in nonsclerainvasion group (25/38, 65.8%) was lower (Plt;0.05) than that in sclerainvasion group (18/20, 90%). The expression of PEDF mRNA was detected in 18/39(46.2) cases, the positive rate in nonsclerainvasion group was higher (Plt;0.05) than that in sclerainvasion group. Conclusions Imbalanced expression of VEGF and PEDF in choroidal melanoma may play a key role in the angiogenesis, tumor progression and metastasis.
Objective To evaluate the application value of scanning laser angiography with a wide-field contact lens system in the diagnosis of choroidal melanoma. Methods Twenty-four patients with choroidal melanoma were randomly divided into two groups, who underwent fundus fluorescein angiography and indocyanine green angiography scanning with the wide-field contact and non-contact lens system respectively in order to acquire the 150deg;wide-field and 30deg;view image data. The quality of the images was comprehensively evaluated. Results Satisfying images were acquired from all of the 24 patients. Widefield contact lens system indicated the accurate adjacent relation between the lesion position and the other dissection mechanisms, and also provided the general information about the size of the tumor and the perfusion of fluorescien or indocyanine green in the blood vessels. At the same time, it enlarged the view scope 3-5 times, which make for the screening of the peripheral lesions. Conclusions Scanning laser angiography with a wide-field contact lens system has important application value in the diagnosis of choroidal melanoma. (Chin J Ocul Fundus Dis, 2006, 22: 166-169)
Objective To evaluate the clinical and histopathological features of diffuse choroidal melanoma. Methods The clinical and histopathological data of 11 patients with diffuse choroidal melanoma were reviewed retrospectively. Those patients were referred to Tianjin Eye Hospital because of visual loss or ophthalmalgia (10 cases), or Coats disease with secondary glaucoma and atrophy bulbi (1 case). The clinical disgnosis included choroidal tumor or melanoma (8 cases), absolutestage glaucoma (2 cases) and atrop hy bulbi with Coats disease (1 case). Nine patients received enucleation, and 2 patients received enucleation combined with orbital exenteration. The cellular proliferation was assessed by Ki-67staining. Results All 11 tumors had grown flatly with a wide base ranged from 12 to 20 mm, and tumor thickness ranged from 2 to 4 mm. There were 9 cases of mixed cell type, 1 case of epithelioid cell type and 1 case of necrotic cell type. The tumors invaded into the sclera in 7 cases and orbital cavity in 3 cases. Secondary glaucoma was found in 7 cases. On average, 9% (7%13%) of tumor cells were Ki67 positive and most of them located at the tumor base. There were more Ki67 positive epithelioid tumor cells than Ki67 positive spindle-shaped cells. Conclusions Diffuse choroidal melanoma had a special growth pattern and is difficult to be recognized, sometimes could be misdiagnosed as glaucoma or other choroidal tumors. With its wide base, this tumor could easily invade the orbit and metastate, and its prognosis is very poor.
Objective To evaluate the role of the cell cycle related genes cyclinD1 and Bcl-2 protein expression in the pathogenesis and infilt ration of the uveal melanoma． Methods Using immunohis tochemistry to detect the cyclinD1 and bcl-2 protein expression in 96 cases of uveal melanoma． Results The expression content of bcl-2 was high in uveal melanoma, and there wasn't any relationship between bcl-2 cell positivity and tumor cell type and extrascleral extension． In contrast, cyclinD1 expression was higher in epithelial cell uveal melanoma than mix cell and spindle cell varieties． There was a positive correlation between cyclinD1 cell positivity and extrascleral extension． Conclusion The expression of bcl-2 protein is important for the survival of the uveal melanoma． CyclinD1 may serve as a sensitive index of its malignancy． (Chin J Ocul Fundus Dis, 2001,17:44-46)
Objective To observe the therapeutic effect of plaque radiotherapy (PRT) on choroidal melanoma. Methods PRT was performed on 21 patients (21 eyes) with chroidal melanoma who had been examined by ophthalmoscopy, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and B-scan echography. The visual acuity was le;0.05 in 3 eyes, 0.06-0.2 in 4 eyes, and ge;0.3 in 14 eyes before the treatment. Choroidal melanoma, round or oval brown solid hunch, was located at the area around macula in 7 eyes, around the optic disc in 7 eyes, at or near the vascular arcade in 5 cases, and at the periphery in 2 eyes. The maximum length、width and thickness of tumor was 13 mm, 11.6 mm, and 9.59 mm. The isotope we used was125I, and the quantum of designed radiation was 100-120 Gy. Fourteen patients with choroidal melanoma at the macular area or around the optic disc underwent plaque radiotherapy associated with transpupillary thermotherapy (TTT). The average follow-up duration was 12 months with the longest duration of 3 years. The basis and thickness (height) of tumors were measured by B-scan echography. The aggrandizement of the tumor would be regarded if the height increased 15% or the basis boundary aggrandized 250mm. Results The visual acuity after the treatment decreased in 9 eyes, remained unchanged in 10, and increased in 2. The dimension of tumo increased in 6 eyes, remained unchanged in 12, and decreased in 3. The complication was vitreous hemorrhage in 2 eys, vascular occlusion in 1, branch retinal venous occlusion in 1, macular pucker in 1, retinal hemorrhage in 3, partial optic atrophy in 3, neovascular glaucoma in 1, and extraction of eye in 3. Conclusion The domestic plaque design is effective on choroidal melanoma, and is of a sort on the thick tumor and the tumor located at macula or beside the optic disc. (Chin J Ocul Fundus Dis, 2006, 22: 157-160)
Objective To investigate the effects of adenovirus-mediated melanoma differentiation-associated gene-7 (mda-7)/IL-24 and/or adriamycin (ADM) on transplanted human hepatoma in nude mice and to explore a new way for hepatoma gene therapy combined with chemotherapy. Methods The recombinant adenovirus vector carrying Ad.mda-7 was constructed; Ad.mda-7 and/or ADM were injected into the tumor-bearing mice. Their effects on the growth of the tumor and the survival time of the mice were observed. The expressions of VEGF and TGF-β1 were detected by an immunohistochemistry method. Results Ad.mda-7 was constructed and expressed in vivo successfully. Compared with other three groups 〔control group (43.4±1.67) d, ADM group (64.2±4.14) d, Ad.mda-7 group (61.4±1.67) d〕, the mice treated with Ad.mda-7 combined with ADM had longer average survival time 〔(83.8±4.82) d, P＜0.01〕; the average size of tumor treated with Ad.mda-7 combined with ADM diminished significantly compared with that treated with ADM or Ad.mda-7 separately (P＜0.01). VEGF and TGF-β1 expressions of Ad.mda-7 group were (56.2±7.7)%, (35.2±4.5)%, respectively, and were lower than those in ADM group (VEGF: P＜0.05; TGF-β1: P＜0.01). VEGF expression of Ad.mda-7+ADM group was (37.3±5.0)%, and was significantly lower than that in other three groups (P＜0.01). TGF-β1 expression of Ad.mda-7+ADM group was (31.2±3.1)% and significantly lower than that in control group and ADM group (P＜0.01), however, there was no significant difference compared with Ad.mda-7 group (Pgt;0.05). Conclusion Ad.mda-7 combined with ADM has b antitumor potency and synergistic effects and suppresses the growth of human HCC xenograft in nude mice, possibly by inducing the apoptosis of hepatoma cell lines and suppressing tumor angiogenesis.
Objective To observe the therapeutic effects and security of the local resection for uveal melanoma, and to detect the factors which affect the prognosis. Methods The clinical data of 45 patients with uveal melanoma who had undergone local resection after examined by histopathology were retrospectively analyzed, including the age，sex，the longest diameter, the location of the tumor，with or without retinal detachment, intraocular pressure (IOP) and visual acuities before and after the operation, and the visual acuity. The relationship between the therapeutic method and the survival prognosis was analyzed. COX regression model was set up with knubbly metastasis relapse prognosis and the multiple factors which was the assistive variables. Results Among these factors, the metastasis and relapse had obvious relation to the longest diameter and height of the tumor(P=0.04), the IOP after operation(P=0.03), pathologic classification (P=0.04)、with or without scleral infiltration (P=0.03)、the location of the tumor (P=0.01) and complete or incomplete resection (P=0.00). The period when the metastasis and relapse of tumor were most likely to happen was 20 to 40 months. Conclusion Local resection is one of the effective methods for uveal melanoma. These patients should be followed up closely from 20 to 40 months after operation, and if necessary, should be treated combined with other treatments. (Chin J Ocul Fundus Dis, 2006, 22: 154-156)
Objective To establish a new model of orthotopic-transplatation tumor of human malignant choroidal melanoma. Methods pEGFP-N1, the eukaryotic expressive plasmid of green fluorescent protein (GFP), was transfered into human malignant choroidal melanoma cell line (OCM-1) by liposome lipofectanine, then the cell clones with stable GFP expression were screened out by means of neomycin, fluorescence microscope, and flow cytometer. Two μl cell suspension of OCM-1 cells with GFP expression with the density of 4.5×107-5.5×107 cells/ml was injected into the subretinal space of right eyes of 40 nude mice (40 eyes) under binocular operating microscope with left eyes as the control ones. The growth of the transplanted malignant choroidal melanoma was observed in vivo using the fluorescence stereomicroscope. The mice were killed at different time after the operation to observe the metastasis of the tumor to optic nerve, brain and other organs including lung, liver, kidney and spleen. Moreover, pathological detection and immunohistochemical staining of GFP was carried out. Results At the postoperative 10th-12th days, the growths of the transplanted malignant choroidal melanoma with dilated and distorted blood vessels and neovascularization were observed; at the postope rative 20th-22nd days, the melanoma occupied the whole cavity of vitreous body; and at the postoperative 24th-26th days, the transplanted tumor grew out of the eye. Metastases of the carcinoma to olfactory bulb, kidney, lung and liver were seen at the failure phase soon after the extra-ocular phase. The histopathological characteristics of the transplanted tumor were similar to those of human, and the results of immunohistochemical staining showed positive expression of GFP in the tumor cells. Conclusion The orthotopic model of malignant choroidal melanoma set up via injection of human malignant choroidal melanoma cells labeled by GFP into the subretinal space of nude mice may provide a new approach to investigate the natural courses of growth and metastasis of malignant choroidal melanoma. (Chin J Ocul Fundus Dis，2004，20：245-248)