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.
Despite its low incidence, retinoblastoma and its rela ted gene (Rb gene) have attracted some of the most brilliant minds in medicine and biology fi elds over the past years. Great advances have been achieved in the tumoregenesis mechanism and clinical management of retinoblastoma recently. However as always , more questions arise from those results. In order to improve retinoblastoma re search in China, we need to strengthen the communication and cooperation with di ffe rent countries, different institutes and disciplines, and utilize the great reso urces of retinoblastoma patients in China.
Children with retinoblastoma (RB) typically survive their cancer due to advances in early diagnosis and treatment. Extraocular invasion and metastasis, and secondary malignant tumor carry a very high mortality rate. Prerequisites for metastasis include tumor initiating capacity, altered cellular adhesion and cell motility, resistance to extracellular death signals and disruption of the basement membrane and extracellular matrix. All those changes can be determined by the cell of origin and the genetic instability of the tumor, responding to the multiple layers of pressure such as hypoxia, from the tumor microenvironment or niche. The interaction between tumor cells and the tumor stroma is regulated by several metastasissuppressor proteins and microRNA. This knowledge has important implications for our understanding and the treatment of extraocular spreading of RB.
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)
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.
Purpose To establish orthotopic heterotransplanted model of retinoblastoma(RB)into the vitreous cavity of nude mice for experimental studies of gene therapies in vivo. Methods To prepare the concentrated cell suspensions of human RB cell line HXO-Rb44 and inject them into the vitreous cavities of 10 nude mice(20 eyes).The experimental mice were randomly divided into 2 groups:the first group,5 mice (10 eyes) were injected with 5 mu;l of the cell suspensions,and the second group,5 mice (10 eyes)with 10 mu;l．The transplanted RB was observed by inspection and ophthalmoscopy,and graded semi-quantitatively in vivo.Light and electrone microscopes were used for histopathological examination,ABC immunohistochemical methods for NSE and GFAP,and flow cytometric investigations for DNA index(DI) and s-phase fraction (SPF). Results All of the models of RB were successfully established by injecting the cell suspensions of human RB cell line into the mice vitreous cavities.The immunohistochemical reaction of the transplanted tumor cells to NSE was positive,and negative to GFAP．The DNA index was found to be more than 1.1,and the determination of SPF indicated the presence of proliferative ability of the transplanted RB cells. Conclusion The above findings reveal that the transplanted tumor cells were similar to those of the parent cells,hence the orthotopic heterotransplantation of RB via nude mice vitreous cavity injection is a superior method in establishing the animal model for the further experimental studies of gene therapies in vivo. (Chin J Ocul Fundus Dis,1998,14:144-148)