[Effects of cisplatin on telomerase activity of human choroidal melanoma cells].

OBJECTIVE: To study the effects of CDDP (cis-dichlorodiamine platinum) on the telomerase of human choroidal melanoma cells and to investigate the toxic effects of CDDP on these cells. To study the relationship between these two effects and to explore the possibility of using CDDP in the chemotherapy of choroidal melanoma. METHODS: It was an experimental research. CDDP was added to the culture medium of primary cultured human choroidal melanoma cells at different concentrations (0.01, 0.1, 1, 10 and 100 mg/L, 72 h) and times (12, 24, 48, 72 and 96 h, 10 mg/L) and the results were compared with that of the controls. Toxic effects of CDDP were evaluated by MTT test and the level of telomerase was measured by PCR-ELISA assay. The correlation between these two effects was analyzed. RESULTS: The telomerase activity was inhibited by CDDP time dependently and dose dependently. Cell viability was decreased when the concentration of CDDP attained 0.1 mg/L and acted for 24 hours. The cell toxicity of CDDP was correlated negatively (r = -0.900, P = 0.037) with the inhibition of telomerase. The cell death was lagged behind the decrease of telomerase. CONCLUSIONS: CDDP is an effective telomerase inhibitor which can decrease the telomerase activity of cultured human choroidal melanoma cells significantly. This effect is dose and time dependent. CDDP can also cause the death of cultured melanoma cells.

[A preliminary study in establishment of mice model of experimental uveal melanoma].

OBJECTIVE: To explore the methods to establish a nude mice model of experimental uveal melanoma by the implantation the primary cultured cells into anterior chamber or subcutaneous injection. METHODS: 35 nude mice, which applied with the SPF grade standard by national healthy department, were divided into 3 groups: anterior chamber group (15), subcutaneous A group (10) and subcutaneous B group (10), respectively. (2 - 3) x 10(5) melanoma cells were inoculated into the anterior chamber of each nude mouse, while 2 x 10(6) cells were inoculated into every subcutaneous of the hind legs in A group. Besides this, the fresh mass of the tumor come from enucleated eye were transplanted into every subcutaneous of the hind legs in B group. Then the condition of transplanted tumor were observed under the slit lamp and naked eye, all nude mice were followed for 3 months the rates of tumor induction were compared. RESULTS: The results of the rates of tumor induction in the 3 groups were 7 (46.6%) of 15, 2 (20%) of 10 and 0 of 10, respectively. The discrepancy were of significance (chi(2) = 7.080, P = 0.029). CONCLUSIONS: Uveal melanoma can be induced successfully by inoculation the primary cultured human uveal melanoma cells into anterior chamber or subcutaneous in nude mice. The results suggest that the ration of the tumor growth is higher in subcutaneous mass transplant than any other groups.

[Clinical analysis of orbital metastasis from nasopharyngeal carcinoma].

OBJECTIVE: Metastasis of nasopharyngeal carcinoma (NPC) to the orbit has been rarely known. We report 11 patients with metastasis of NPC to the orbit and discuss their clinical characteristics and prognosis. METHODS: Eleven patients with orbital metastasis of NPC who were seen between January 1, 1991 and December 31, 2003 in Zhongshan Ophthalmic Center, Sun Yat-sen University, were retrospectively reviewed. RESULTS: Among 11 patients, there were nine males and two females. The mean age at diagnosis was 45.5 years. The left eye was involved in ten cases, and right eye in one. There were seven patients with a known history of NPC and four with no NPC history at the time of presentation. The seven patients with NPC history developed orbital metastasis at a mean time of 12.7 months (range 2.0 - 60.0 months) after the diagnosis of NPC. The mean duration of eye lesions at presentation was 10.3 months (range 0.7 - 36.0 months). Nine patients developed single metastatic focus and two patients had two foci in the affected orbit. The main component of the tumor was located in the nasal part of the orbit in eight cases, in the temporal part in two, and in the orbital apex in one. The anterior part of the orbit was affected in eight cases. The neoplasm was resected completely or partly through surgery. The diagnosis was histopathologically confirmed as NPC. Among them, four cases were squamous cell carcinomas, two cases lymphoepitheliomas, and five cases unclassified carcinomas. At the last following up examination, five patients had died as a result of disseminated metastasis, one patient had died of unknown cause and three were still alive with no active metastasis. Two patients had lost follow-up. The mean survival time after orbital diagnosis was 21 months. CONCLUSIONS: NPC with orbital metastasis is rare. However, it is the most common primary cancer metastasizing to the orbit in our Center. Most of them were located in the anterior nasal part of the orbit. The prognosis of these metastasis cases is very poor.

[Diagnosis and surgical management of 209 cases of orbital cavernous hemangioma].

OBJECTIVE: To study the clinical features, preoperative diagnosis and surgical choice of orbital cavernous hemangioma. METHODS: Records of all cavernous hemangioma patients (209 cases) who were seen in Eye Hospital, Zhongshan Ophthalmic Center, Sun Yat-sen University from January 1, 1986 to December 31, 2000 were reviewed. RESULTS: Among 209 cases, 123 patients were females and 86 were males. The left orbit was affected in 123 cases and the right orbit in 86 cases. No case was bilaterally involved. The mean age was 39.2 years old, ranging from 5 to 68 years. A painless, gradually progressive proptosis and visual disturbance were the main clinical signs. Ninety-five percent (199/209) of them could be accurately diagnosed preoperatively based on ultrasound scan and CT/MRI examination. The tumors were removed successfully by the surgical procedure of standard lateral orbitotomy in 36% (75/209) of patients and anterior orbitotomy in 64% cases (134/209). CONCLUSIONS: Nearly all patients with cavernous hemangioma could be correctly diagnosed by preoperative image studying. The simple surgical procedure of anterior orbitotomy can be successfully used in about two third of cases with less surgical complication.

[Emphasizing the fundamental and clinical research on thyroid-associated ophthalmopathy].

In this article, we discussed the pathogenesis and current status of the research in thyroid-associated ophthalmopathy (TAO). TAO, the most common orbital disease in adults, is an orbital autoimmune disease closely related to Graves' disease. Now, the fundamental and clinical research on TAO should be further enhanced.

[Clinical analysis of 339 cases of thyroid-associated ophthalmopathy].

OBJECTIVE: To summarize the clinical manifestation of thyroid-associated ophthalmopathy (TAO), to analyze the thyroid function and to monitor the therapeutic effect of anti-hyperthyroidism on the progression of TAO. METHODS: Three hundred and thirty nine TAO cases (597 eyes) were collected from 1994 to 2001 and their clinical manifestations were summarize and analyzed. RESULTS: TAO occurred mostly in individuals over 40 years with no gender preference. Exophthalmos and diplopia were the major manifestations and main reasons for ophthalmic examination. Retraction of eyelids and involvement of extraocular muscle were present in over 70% cases. In 339 TAO cases, euthyroidism was found in 93 cases and abnormal thyroid function (hyperthyroidism or hypothyroidism) was present in 246 cases. The V and VI grade of TAO occurred more frequently in patients with abnormal thyroid function than those with euthyroidism. (131)I, oral anti-hyperthyroidism drug, or thyroidectomy was used for all patients with abnormal thyroid function. TAO occurred in 39.3% cases treated with (131)I, in 15.6% cases with oral anti-hyperthyroidism drug, and in 14% cases with thyroidectomy. All ocular pathologic changes occurred after hyperthyroidism had been controlled and hypothyroidism was found in most of these cases. CONCLUSIONS: The condition of thyroid function has a certain relationship to the severity of TAO. Over-fast and undue anti-hyperthyroidism therapy may impact an untoward effect on TAO; immediate and appropriate treatment can improve the effect of therapy on TAO.

[Effect of bcl-2 antisense oligonucleotides on multidrug resistance of cultured uveal melanoma cells].

OBJECTIVE: To evaluate the chemotherapeutic sensitivity of uveal melanoma in vitro and reverse its drug resistance by the delivery of bcl-2 antisense oligodeoxynucleotide (AS-ODN). METHODS: The drug sensitivity tests of primary cultured uveal melanoma cells toward 5-flurouracil (5-FU), thiophosphamide (TSPA), cisplatin (DDP), adriamycin (ADM), vinblastine (VLB), dacarbazine (DTIC) were performed with 3, -4, 5 dimethyliazol-2,5 diphenyl tetrazolium bromide (MTT). AS-ODN bcl-2 were delivered with cationic lipid to down-regulate bcl-2 expression. Immunohistochemistry and Western-blot methods were used to detect bcl-2 expression. According to the principle of multi-drug mutual action, the influence of anti-apoptosis gene bcl-2 on tumor cell drug sensitivity was measured. RESULTS: Uveal melanoma was resistant to different chemotherapeutic drugs in different degrees. AS-ODN bcl-2 could down-regulate bcl-2 expression, was synergetic with all tested drugs and partially reversed the multi-drug resistance. CONCLUSIONS: Clinically, with ordinary dosages the above 6 drugs have little cytotoxicity to uveal melanoma cells, bcl-2 over-expression is associated with multi-drug resistance and AS-ODN bcl-2 can partially reverse the multi-drug resistance.

[Clinical analysis of tumors of the iris and ciliary body].

OBJECTIVE: To evaluate the clinical features, different diagnosis, pathological features, management, and prognosis of tumors of the iris and ciliary body. METHODS: Medical records, photographs, pathological findings and the results of follow-up of 37 cases with tumors of the iris and ciliary body were reviewed as a retrospective study. RESULTS: Of the 37 cases with tumors of the iris and ciliary body, 26 were male and 11 were female. The mean age at diagnosis was 38 years, ranged from 5 - 64 years. According to the histopathological examination, melanoma was the most common tumor in the iris and ciliary body (15 cases, 40.5%), followed by metastatic tumors (8 cases, 21.6%), teratoid medulloepitheliomas (3 cases, 8.1%) and iris nevus (2 cases, 5.4%). MANAGEMENT: The tumors were excised in 14 cases. Enucleation was performed in 21 cases. Two cases were observed without any surgical treatment. Thirty-four cases were followed-up for 2 months to 15 years, averaged 31 months. Most melanomas of the iris and ciliary body are round or semi-spherical dark brown vascularized mass, with engorged episcleral sentinel vessels in some cases. The tumor showed a shadow during transillumination. Ultrasound biomicroscopy revealed a low to medium echoic solid lesion, with echoic changes in adjacent infiltrated tissues. Melanoma showed positive immunoreactivity for melanoma-specific antigen, and had a good prognosis. Metastatic tumors of the iris and ciliary body were flat or near round, dirty, single or multiple neoplasms, growth rapidly, with abundant neovascularization, and had a poor prognosis. Primary carcinomas could be found in other parts of the body. CONCLUSIONS: Melanoma of the iris and ciliary body has typical features that may help to distinguish them from other tumors. Metastatic tumor has characteristic features, but the diagnosis can be made only with supplementary examination and immunocytochemical studies. Medulloepitheliomas should be differentiated from retinoblastoma.

[The inhibition effect of interleukin-1 receptor antagonist on interleukin-1 alpha-induced intercellular adhesion molecule-1 expression on orbital fibroblasts and adhesion of peripheral blood mononuclear cells].

OBJECTIVE: The aim was to identify whether interleukin-1 receptor antagonist (IL-1ra) inhibits interleukin-1 alpha (IL-1 alpha)-induced intercellular adhesion molecule-1 (ICAM-1) expression on cultured orbital fibroblasts, and adhesion of peripheral blood mononuclear cells (PBMC) to orbital fibroblasts, and to investigate the clinical application potential of IL-1ra in the treatment of Graves' ophthalmopathy (GO). METHODS: Cultured orbital fibroblasts from patients with GO and controls were challenged with IL-1 alpha or/and IL-1ra. Immunocytochemical staining was used to examine the changes of ICAM-1 in response to IL-1ra treatment; fluorescent photomicroscope was used to measure the adhesion between the labeled PBMC and orbital fibroblasts. Neutralizing antibody against ICAM-1 was used to demonstrate the role of ICAM-1 in the IL-1 alpha-induced adhesion. RESULTS: IL-1ra inhibits IL-1 alpha-induced ICAM-1 expression in cultured orbital fibroblasts both from GO patients and controls; IL-1ra inhibits IL-1 alpha-induced adhesion of PBMC to orbital fibroblasts in a concentration and time dependent manner. Moreover, a monoclonal anti-human ICAM-1 antibody produced a concentration dependent inhibition of the IL-1 alpha-induced adhesion of PBMC to the fibroblasts. CONCLUSIONS: IL-1ra inhibits IL-1 alpha-induced ICAM-1 expression in cultured orbital fibroblasts and the adhesion of PBMC to fibroblasts. IL-1 alpha-induced ICAM-1 expression may play an important role in the adhesion process. IL-1ra may be useful in the prevention or treatment of GO.