Stem cells are crucial for embryonic development and in the maintenance of adult cellular homeostasis. Understanding the regulatory network of stem cells, including embryonic and adult stem cells, will allow us to learn the pathogenesis and possibly design novel approaches to treat many diseases (such as cancer and degeneration). The retinoblastoma (Rb) pathway controls cellular proliferation, differentiation and death. More and more evidences support an important role of Rb activity in the biology of stem and progenitor cells. Transiently inactivating Rb pathway might favor the expanding of functional stem cell populations, thus have values in the future stem cell applications.
Microparticles are small vesicles that are released by budding of the plasma membrane during cellular activation and apoptotic cell breakdown. A spectrum of cell types can release microparticles including endothelial cells, platelets, macrophages, lymphocytes and tumor cells. Biological effects of microparticles mainly include procoagulant activity, inhibition of inflammation and cancer progression. The present study shows that vitreous microparticles isolated from proliferative diabetic retinopathy (PDR) stimulated endothelial cell proliferation and increased new vessel formation, promoting the pathological neovascularization in PDR patients. Oxidative stress induces the formation of retina pigment epithelium-derived microparticles carrying membrane complement regulatory proteins, which is associated with drusen formation and age related macular degeneration. Microparticles from lymphocyte (LMP) play an important role in anti-angiogenesis by altering the gene expression pattern of angiogenesis-related factors in macrophages. Besides, LMP are important proapoptotic regulators for retinoblastoma cells through reduction of spleen tyrosine kinase expression and upregulation of the p53-p21 pathway which ultimately activates caspase-3. However, how to apply the microparticles in the prevention and treatment of retinal diseases is a major challenge, because the study of the microparticles in the fundus diseases is still limited. Further studies conducted would certainly enhance the application of microparticles in the fundus diseases.
The debate on the cell of origin of human retinoblastoma lasted for more than one century. In the recent issue of ldquo;cellrdquo;, David Cobrinikprime;s group shows that L/M cone precursors are the most likely answer as they have an intrinsic circuitry, including murine double minute 2 (MDM2), Nmyc, the nuclear receptors retinoid X receptor and thyroxine receptor 2, making them extremely sensitive to transformation following retinoblastoma gene inactivation.
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.
A review of 426 patients with retinoblastoma(RB)who presented to Eye Hospital of Zhongshan Ophthalmic Center from 1966 to 1991 showed that 81(19.01%)patients were more than or equal to 5 years of age(median age 6.95 years)at the time of initial diagnosis.All patients are unilateral except 4 cases who are bilateral.The main presentations included leukocoria,exophthalmos,congertion and pain of the eye,drcreased vision,strabismus,oculare hypertension,vitreous opacity,hypopyon and hyphema,etc.Some atypical presentations in these older patients with RB were discussed and some problems that should be noticed in the diagnosis and management were presented.discussed and some problems that should be noticed in the diagnosis and management were presented.
（Chin J Ocul Fundus Dis,1993,9:205-206）
PURPOSE:Studying the multidrug resistance(MDR) phenotype occurring in retinoblastoma and its mechanism.
METHODS:Using the procedure of stepwise increase in drug concentrations to obtain a retinoblastoma subline which resistant to 600ng/ml vincristine (HXO-RB/VCR). Characteristics of this drug-resistant cell line were investigated by cell
counting,drugcontents determinatin,drug sensitivity evaluation and radiation sensitivity test. RESULTS:This cell line was cross-resistant to VDS,MMC VP16，ADM ,DDP,CBP,but not resistant to BCNU and 5-Fu. It was proved to be collaterally sensitive to MTX,and the response to 60Co gamma;-ray was modified slightly in HXO-RB/VCR cell line. Intracellular levels of VCR was much higher in HXO-RB44 cells than in the resistant subline. Those cross-resistances can be reversed by verapamil partly.
CONCLUSIONS:MDR and radiation resistance of retinoblastoma can be induced by exposing to VCR and reversed by verapamil partly.
（Chin J Ocul Fundus Dis,1997,13: 6-9）
The studies of immunohistochemistry, histochemisu3r and electron microscopy in 50 patients with retinoblastoma were carried out. Our results show that retinoblastoma origin from primitive retinal neuronal cells that can differentiate into nmture neuron (including retinal photoreeeptor) and glial cells.The glial component in the retinoblastoma is mainly reactive glial proliferation.There is a good prognosis in the patients with retinoblastoma in which there are a lot of differiation areas and glial proliferation.
（Chin J Ocul Fundus Dis,1993,9:193-197）
ObjectiveTo observe the effect of systemic chemotherapy on conditions of tumor infiltrating,metastasis and disease-specific survival (DSS) for advanced retinoblastoma (RB).
MethodsForty-one patients with advanced RB who received enucleation were enrolled in this study. There were 26 males and 15 females, age at diagnosis was ranged from 2 to 72 months, with a mean of 23.08 months. There were 16 bilateral patients and 25 unilateral patients; 13 group D eyes and 28 group E eyes. 16 patients received enucleation as the primary treatment (operation group), 25 eyes received chemotherapy before enucleation (chemotherapy group). There was no significant statistical difference between two groups for the gender, unilateral and bilateral, international staging or diagnostic age (P>0.05). The histopathology report was performed to assess the risk of postoperative tumor-node-metastasis staging (pTNM) in each patient, and the extent of tumor invasion in the optic nerve, choroid and anterior chamber was divided into 3 levels of low risk, medium risk and high risk. Five deaths were all in the group E with chemotherapy before enucleation. Using R software survival analysis software package survfit function, the application of Kaplan-Meier estimation method, DSS of RB children was calculated from the time of diagnosis, up to the date of the death of patient. DSS differences between chemotherapy, operation group and eye removal time (more than 3 months, less than 3 months) in group E RB children were analyzed.
ResultsThe proportion of high risk pTNM stage in chemotherapy group was significantly lower than the operation group. But there was no significant difference between the two groups in the overall risk classification (χ2=3.130,P=0.077). For group D eyes, the overall risk classification in chemotherapy group was significantly lower than the operation group (χ2=5.870,P=0.015). There was no significant difference between the two groups in the overall risk of group E eyes (χ2=0.020,P=0.889). The DSS in chemotherapy group and operation group were 0.71 and 1.00, respectively; the difference was significant (χ2=3.700,P=0.05). The DSS in children whose enucleation delayed for more than 3 months and children whose enucleation performed within 3 months were 0.64 and 1.00, respectively; the difference was significant (χ2=4.800,P=0.028).
ConclusionSystemic chemotherapy did not reduce the risk of tumor invasion and metastasis in patients with advanced RB. Instead, it will reduce the DSS in group E eyes of RB.
Nowadays, one of the most challenging aspects of retinoblastoma (RB) therapy is how to control the resistant or recurrent viable vitreous seeds, for which intravenous chemotherapy appears to be ineffective. Recently, intravitreal chemotherapy offers another option to control advanced stage and vitreous seeds of RB, and may be a promising new approach to RB therapy. However, intravitreal injection for RB patients raises considerable controversy due to concerns of possible extraocular extension along the injection route, and should not replace the primary standard of care for bilateral RB or group E eyes of RB. Close follow-up and further studies are needed to determine appropriate indications, to determine the effective drugs and concentrations, to optimize RB therapy protocols and to investigate the relationship between long-term efficacy and toxicities.
Purpose
To investigate nucleoside diphosphate kinase (NDPK ) expression of tumor metastasis suppressor gene nm23 in heterotransplanted model of retinoblastoma(RB) in nude mice，and analyse the correlation between the expression of nm23 gene and the formation and progression of heterotran splanted RB．
Methods
SP immunohistochemical method was used to detect the expression of nm23 gene product NDPK in 20 tumors of heter otransplanted RB model and normal retinal tissue．
Results
The negative staining of nm23/ NDPK was found in normal retinal tissue , whereas 100% expression rate in RB tumors with positive number of 48.73plusmn;2.37． No statistical significance of the expression of nm23/ NDPK was observed between the intraocular growth phase （I～Ⅲ grade） and invasive phase （ Ⅳ～Ⅴ grade）in heterotransplantedRB tumors．
Conclusion
The function of nm23 gene as a tumor metastasis suppressor in heterotra nsplanted RB tumors was less prominent ,but it may play a role in carcinogen esis and progrssion of RB and may predict poor prognosis．
(Chin J Ocul Fundus Dis, 2001.17:47-49)
