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Retinoblastoma (RB) and choroidal malignant melanoma are the most common primary intraocular malignancy in children and adults, respectively.Due to the advance in the diagnosis and treatment of intraocular tumors, the survival rate and survival time of the patients are significantly improved.The goal of the therapy for the patients of intraocular malignant tumors has gradually changed from simply saving life to trying to preserve eyeball on the basis of saving life.Although there are various treatment options for intraocular malignant tumors, eye salvage is still an great challenge for the patients with refractory tumors.In recent years, vitrectomy has been used again by some doctors to the treatment of refractory RB and choroidal malignant melanoma, which undoubtedly gives the hope of eye salvage to the patients with intraocular malignant tumors.However, this therapy arouse controversy because serious intraoperative or postoperative complications occurred in some patients.Ophthalmologists should select suitable indications for this surgery cautiously, perform the operation carefully, combine other chemotherapy and/or radiotherapy and local treatment and close follow-up if necessary.
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Retinoblastoma (RB) is the prototype of hereditary neoplasms in humans.It is the most common intraocular malignancy in children,which is mainly caused by RB1 gene mutation.RB1 genetic testing and genetic counseling supports optimal care and follow-up plan for RB patients and their families.RB is the first cancer to officially acknowledge the seminal role of genetics in cancer,by incorporating "H" into the eighth edition of cancer staging (2017);those who carry the RB1 cancer-predisposing gene are H1;those proven to not carry the familial RB1 mutation are H0;and those at unknown risk are HX.However,due to the complexity of RB1 gene mutation,the limitation of current genetic test,the lack of genetic counseling specialty,there is limited application of genetic testing and counseling in China.In the era of precision medicine,we need to advocate the application of RB1 genetic testing in the management of RB patients in China.
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Diabetic retinopathy (DR) is a common complication of diabetes,and remains the leading cause of blindness among working-age individuals all over the world.Current treatments for DR mainly focus on the advanced stages of the disease and are associated with significant adverse effects.As the pathogenesis of DR is not thoroughly revealed,the development of more effective therapy of DR is challenging,in which a good DR animal model is essential.At present,these animal models involve mammals,non-mammals and other species.The modeling methods also include chemical injection,high glucose diet,genetic engineering and ex vivo retinal explant cultures.Although most of the models discussed,especially the rodent models,have demonstrated the basic features of NPDR,the key feature of human PDR (pre-retinal neovascularization secondary to diabetes per se) is not recapitulated in any diabetic animal models.Therefore,choosing the appropriate DR animal model according to the purpose of research will be very important in understanding development of the disease and new approaches that prevent or delay the onset of DR.
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Retinoblastoma (RB) therapy has evolved over decades.In the 1970s, enucleation was important for improving life prognosis.In the 1980s, external beam radiotherapy (EBRT) was popular.In the 1990s, systemic intravenous chemotherapy (IVC) was introduced and currently remains prevalent worldwide for intraocular RB control as well as prevention of systemic metastasis.However, RB seeds in vitreous and subretinal space are still the major obstacles for successful treatments.Advanced ophthalmic imaging technology promotes thorough and detailed description and observation of RB seeds.In the 2000s, interests in periocular chemotherapy (POC), intra-arterial chemotherapy (IAC) and intravitreous chemotherapy (IVitC) have been explored to overcome the low drug concentration around the seeds and to reduce the systemic side effects.This leads us into a new era of target local chemotherapy of RB.How to make the treatment decision based on biological behavior of RB seeds is a major task for us now.
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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.
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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.
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The debate on the cell of origin of human retinoblastoma lasted for more than one century.In the recent issue of "cell",David Cobrinik'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),N-myc,the nuclear receptors retinoid X receptor and thyroxine receptor 2,making them extremely sensitive to transformation following retinoblastoma gene inactivation.
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BACKGROUND:Hepatocyte growth factor(HGF) is a kind of multifunctional growth factor,which can accelerate cell growth,transition and genesis in various organs.In cardiovascular system,HGF has reported to have anti-apoptotic,anti-fibrotic,as well as repair endothelial cell injury effects,suppose that HGF has relationships with hypertension.OBJECTIVE:To investigate the effect of HGF on blood pressure,vascular endothelial system and renin-angiotensin system(RAS) in spontaneously hypertensive rats,further more,to discuss the mechanisms between HGF and hypertension.DESIGN,TIME AND SETTING:The randomized control experiment on animal was performed at the Department of Cardiology,First Affiliated Hospital of Anhui Medical University from March to July 2007.MATERIALS:The exogenous HGF power was purchased from America Peprotech Company.Rats with 14-weeks-old,weighting 200-250 g,were randomly divided into the experimental and spontaneous hypertension groups,WKY rats were serves as the control group,with 12 animals in each group.METHODS:Rats in the experimental group were administrated 5,10,15,20,and 25 ?g/kg HGF per 24 hours,the partes aequales sodium chloride was injected into the spontaneous hypertension and control groups.Five minutes after administration,systolic pressure and heart rates were measured.The rats were sacrificed and harvested 2 mL blood of right ventricle when blood pressure decrease the lowest,about 30 minutes after administration.MAIN OUTCOME MEASURES:The effect of HGF on systolic pressure and heart rates,and levels of serum nitrogen monoxidum(NO),plasma endothelin(ET),as well as angiotensinⅡ(Ag Ⅱ) were detected by colorimetry and radio-immunity methods.RESULTS:When injected 5?g/kg HGF,the blood pressure did not significantly change.After 10 ?g/kg HGF injection,the blood pressure began to decrease and reached a peak after 30 minutes,gradually recovered after 1 hour,and back to the normal after 5 hours.Injection of 20 ?g/kg has largest effect on rats,with reduced contractive pressure 40-50mmHg,but no significantly changes appeared by adding HGF dose.There were no significantly differences of heat rate and blood pressure between the two control groups.Compared with the spontaneous hypertension group,the levels of ET and AgⅡ were decreased,however,the level of NO was increased(P
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Aim To evalute the effects of losartan on the cardiac function and secretion of nitric oxide(NO) and endothelin(ET) in patients with congestive heart failure(CHF) .Methods Sixty patients with class Ⅱ～Ⅳ CHF were randomised to receive a 12 weeks of routine therapy either with losartan(n ＝ 30)to be added from 25 mg to 50 mg daily or with enalapril(n ＝ 30) to be added from 2.5 mg to 5 mg daily. The cardiac systolic and diastolic funtion and the levels of NO and ET were observed before and after therapy respectively, with 30 normal control subjects seving as control. Results The abnormal cardiac systolic and diastolic function parameter were present in patients with CHF. The ET and NO levels in CHF patients were significantly higher than those in the control group(P＜0.05) . NYHA function class was improved in 85% of losartan-treated patients and in 84% of enalapril-treated patients after 12 weeks, as compared with cardiac function at baseline. ET and NO levels were significantly reduced(P＜0.01), NO/ ET ratio was increased (P＜0.05) after 12 weeks of therapy in two active groups. Conclusion The systolic and diastolic functions of patients with CHF are greatly improved by losartan treatment, which reverses the imbalance of NO/ET and it is suspected that this action may be another important mechanism of its treating heart failure.
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Purpose [WT5”BZ]To estabalish a quantifying model of retinal neovascularization suitable for the study of pathogenesis and therapeutic intervention for the retinal neovascularization. [WT5”HZ]Methods [WT5”BZ]Sixteen one week old C 57 BL/6 mice were exposed to 75% oxygen for 5 days and then to room air and 16 mice of the same age kept in room air as controls.Ink perfused retinal flatmount was examined to assess the oxygen induced changes of retinal vessels.The proliferated neovascular response was quantitated by counting the nuclei of endothelial cells of new vessels extending from the retina into the vitreous in 6 ?m sagittal cross sections. VEGF and bFGF were determined on the cross sections after immunohistochemcal stain. [WT5”HZ]Results [WT5”BZ]Constriction and closure of the blood vessels were found under the hyperoxia condition,and dilation and proliferation were found under the relatively hypoxia status.There was a mean of 24 neovascular nuclei per cross section in the oxygen treated retina and less than 1 nucleus in the control group ([WT5”BX]P
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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 heterotransplanted RB. Methods SP immunohistochemical method was used to detect the expression of nm23 gene product NDPK in 20 tumors of heterotransplanted 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 48.73?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 heterotransplanted RB tumors was less prominent ,but it may play a role in carcinogenesis and progrssion of RB and may predict poor prognosis.