Objective To investigate inhibited effects of melatonin (MLT) on proliferative activity of retinoblastoma cell line HXORB44 and its related mechanism. Methods HXO-RB44 cells were treated by MLT of different concentration (10-10, 10-9, 10-8, 10-7 mmol/L. Cell counting and tetrazolium dyereduction assay (MTT) were used to determine the effect of MLT on the survival and proliferation of HXO-RB44 cells. Apoptotic nuclei were further analyzed by HoechstPI fluorescence staining. Flow cytometry was used to measure the fluorescent intensity of ROS, cell cycle distribution and apoptosis. Results 10 -6 mmol/L (or exceed) of MLT could inhibit the proliferation of HXO-RB44cells in vitro while 10-7 mmol/L (or below) of MLT couldn't. With the increase of MLT concentration from 10-10 mmol/L to 10-7 mmol/L, HXO-RB44 cells gradually increased the expression of ROS. Hoechst staining showed that 4, 8, 12 and 24 hours after the incubation with MLT, the nuclear pyknosis and nuclear fragmentation increased in HXORB44 cells. The extent of apoptosis was proportional to the concentrations of MLT. Flow cytometry revealed that with the increasing of MLT concentration, G0/G1 and G2/M phase cells increased, S phase cells decreased. The apoptotic rate was also increased. Conclusion 10 -6 M of MLT could inhibit the proliferation of HXO-RB44 cells. This effect may relate to the increased ROS expression, cell cycle arrest at G0/G1 phase and apoptosis of HXO-RB44 cells.
Retinoblastoma (RB) is the most common intraocular malignant tumor in children. With advanced clinical technologies there are more and more methods available to treat retinoblastoma, and make it is possible to delivery individualized protocol combined traditional treatments with modern regimen to patients now. In order to improve the survival rate and the life quality of RB patients in China, it is very important to make a suitable system of standardized therapy based on results from developed countries and health policies of our own country.
Objective：To observe the therapeutic ef fect of chemoreduction treatm ent combined with local focal therapy for advanced intraocular retinoblastoma (R B). Methods：Thirteen eyes of nine patients with RB underwent c hemoreduction tr eatment combined with local cryotherapy and (or) transpupillary thermotherapy (TTT), and the clinical data of the patients were retrospectively analyzed. The vi ncristine, etoposide, and carboplatin (VEC) were used in the chemoreduction trea tment. The average followup duration was 15.3 months. Results：All of the 13 e yes with RB had favorable initial reaction in the treatment of chemoreduction. A fter the first period of chemotherapy, the largest diameter of the tumor fundus decreased 37.2%, and the tumor thickness averagely reduced 46.7%. The subretinal fluid was absorbed completely or partially in 6 eyes (6/8); vitreous and subret inal seeds reduced, disappeared or calcified in 10 (10/11) and 11 eyes (11/11), respectively. During the treatment and in the followup duration, 8 eyes (8/13) had new tumors and (or) recurrences. Finally, 2 eyes (2/13) were enucleated whil e 11 eyes (11/13) were saved in which 8 (8/11) recovered or remained good visual acuity. None of 9 patients had serious side effects of chemotherapy like leucoc ythemia, functional damage of liver and kidney, and dysacousia. Conclus ions：Chem oreduction treatment has well initial effect on advanced RB. Chemoreduction trea tment combined with local treatment may effectively control the retinal tumor, s ubretinal seeds and vitreous seeds within a shortterm duration. The evaluation of longterm effect of the treatment needs further observation.
Objective:To observe the therapeutic effi cacy of chemotherapy combin ed with ophthalmic therapy on retinoblastoma (RB). Methods:The survival rate, eye ball remaining rate, and the control of the disease condition of 37 patients (56 eyes) with RB were retrospectively analyzed. The standard of the well contr ol of the disease included: (1) the ocular tumor shrank or even disappeared, and the tumor had creamlike changes or calcification and cicatrisation; (2) no oc u lar tumor recurrence in patients who had undergone enucleation; (3) no metastasi s found in the followup period. All of the patients had at least one eye with RB (ge;Ⅲb stage) underwent c hemotherapy. According to the response of the tumor to the chemotherapy, the pat ients generally underwent 6 times of systemic chemotherapy at regular intervals of 3-4 weeks. The medicines for chemotherapy included vincristine, cyclohosphamide , etoposide phosphate, and carboplatin. According to the self condition, the pati ents underwent chemotherapy combined with several ophthalmic therapies like phot ocoagulation, cryotherapy, transpupillary thermotherapy, 106Ru brachytherapy, en ucleation, etc. The observation duration lasted 2-59 months, with the average o f 35 months. Results:Thirty patients (83.3%) survived and were followed up, and 6 died (16.6%). One patient with bilateral tumor couldn't be followed up afte renucleation of both eyes. Among these 30 patients (45 eyes), eye ball remainin g rate at stage I-Ⅱ, Ⅲ-Ⅳ, and Ⅴ was 100% (10 eyes), 70% (10 eyes), and 14 .3% (21 eyes), respectively. In the followup duration, the disease in all of the 3 0 patients was controlled well. Conclusions:Chemotherapy combi ned with ophthalmic therapy is effective on RB.
Objective To study hyperthermia induced apoptosis and the effect of aspirin on hyperthermia induced apoptosis in retinoblastoma cells. Methods Retinoblastoma cells (Y79) were divided into two groups:hyperthermia groups,hyperthermia+aspirin (0.18～18mu;g/ml) groups.Heat shock condition:44℃,heat shock time:10,20,30, and 40 minutes respectively.The following events were studied after heat shock by using FAC Scan: ①cell apoptosis; ②heat shock protein 70 (HSP70) expression；③bcl-2 expression. Results Apoptosis was induced by the treatment of hyperthermia (44℃) in Y79 cells in a heat dose dependent fashion.Longer time heating (44℃，40 minutes) induced necrosis rather than apoptosis.Aspirin could rescue Y79 cells from hyperthermia induced apoptosis in a dose dependent manner．HSP70 was induced in Y79 cells after heat shock,it was further enhanced by the treatment of aspirin(＞1.8mu;g/ml).Heat shock itself showed no effect on bcl-2 expression in Y79 cells,aspirin,on the other hand,could enhance bcl-2 expression in a modest level in heat treated Y79 cells. Conclusions Hyperthermia may induce apoptosis in Y79 cells which can be protected by use of aspirin．The enhancement of HSP70 and bcl-2 expression in Y79 cells by the treatment of aspirin in heating condition may be responsible for the protective function. (Chin J Ocul Fundus Dis, 1999, 15: 143-145)
Intra-arterial chemotherapy (IAC) is an interventional treatment for retinoblastoma (RB) which infuses the chemotherapeutic agents through ophthalmic artery using microcatheters to control the tumor. Compared with systemic chemotherapy, IAC could significantly increase the globe salvage of advanced and recurrent RB without serious adverse event. Due to the absence of systemic absorption after IAC, no longer effectively kill tumor cell, which have potential danger to leads to inadequate elimination extraocular tumor cells. The most common systemic complications following IAC is myelosuppression; local ocular toxicities include eyelid edema, delacrimation, blepharoptosis, vitreous hemorrhage, retinal artery obstruction. During the last 10 years of clinical application, IAC become one of first-line treatment for intraocular RB. However, at present, there is still a lack of randomized controlled multicenter studies and long-term follow up of IAC.
ObjectiveTo observe the curative effect, survival rate, enucleation rate and pathological characteristics of retinoblastoma (RB) in children.MethodsRetrospective clinical study. From March 1999 to December 2018, a total of 313 patients (445 eyes) with RB diagnosed in Ophthalmology Department of Peking University People’s Hospital were enrolled in the study. Among them, 175 were male (55.9%), 138 were female (44.1%); 181 were monocular and 132 were binocular. The international standard of intraocular RB staging (IIRC) was 6, 13, 6, 52, 227 and 9 patients of A, B, C, D, E and extraocular stages respectively. Among the 313 patients, 245 patients were confirmed to the survivance, of which 22 cases (9.0%, 22/245) died. Among 445 eyes, 330 eyes definitely whether or not were enucleated; 184 eyes had definite IIRC stage, eye examination results, definite treatment plan and times before enucleation and definite pathological tumor node metastasis stage after operation. The basic information, demographic characteristics, clinical information, enucleation and treatment plan, pathological and immunohistochemical results were recorded. Binary logistic regression was used to analyze the risk factors of high risk pathological features (HRF) and prognosis in patients with RB.ResultsFrom 1999 to 2018, the survival rate of 245 patients was increased from 82.6% to 96.3% year by year; the enucleation rate of 330 eyes with final enucleation was reduced from 68.8% to 58.3% year by year. The rate of enucleation in stage D and stage E decreased from 83.3% and 100% before 2005 to 37.5% and 85.4% after 2014, respectively. Monocular disease (β=－1.551, P=0.005), stage D, stage E and extraocular stage in IIRC stage (P＜0.005) were the independent risk factors of RB enucleation, while the protective factors were Interventional chemotherapy of ophthalmic artery (IAC) (β=－0.877, P＜0.001). HRF was found in 51 eyes (27.7%). Age of onset (β=0.019, P=0.016) and glaucoma (β=0.816, P=0.050) were independent risk factors for HRF in RB pathology, while IAC treatment was the protective factor for enucleation (β=21.432, P＜0.001).ConclusionsAfter comprehensive treatment, the general trend of RB enucleation rate is gradually decreasing. IAC treatment can reduce the enucleation rate of stage D and E. The older age of onset and glaucoma stage are the independent risk factors of HRF, and IAC can reduce the risk factors of HRF.
The treatment for retinoblastoma (RB) has been reached the stage of life-saving and vision-saving care. It is necessary to improve the survival rate and prolong the life time of RB children, retaining the eyeball and improving the quality of life. If the diagnosis is not timely and the treatment is inappropriate, the tumor recurrence, extraocular spread and metastasis of retinoblastoma will occur. The rate of eye protection and the survival chance of RB children will be reduced. With the continuous exploration of RB therapy and the emergence of new treatment methods, how to correctly select and evaluate these treatment methods and to adopt the most safe and effective treatment for RB children, to achieve long-term cure effect, is an important problem which clinicians need to consider.