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Cytokine-induced modulation of cellular proteins in retinoblastoma. Analysis by flow cytometry.

Cytokines are a group of specialized, hormone-like proteins that can exert profound influences on cellular development and on a variety of cellular functions. Retinoblastoma cells are an important model for exploring human malignancy and differentiation. These multipotent embryonic cells are capable of differentiating into neuronal, glial-like and retinal pigment epithelium (RPE)-like elements. This report shows that flow cytometric analysis can be used to measure the expression of both cytoplasmic and cell surface proteins in retinoblastoma cells. The authors used this technique to monitor changes in the expression of selected cellular proteins after exposure to specific cytokines and found that MHC class I molecules were augmented by interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma), but not by tumor necrosis factor (TNF). However, the MHC class II molecules were augmented by IFN-gamma but not by IFN-alpha or TNF. The neuronal markers, IRBP and PR-6, the glial-like marker, GFAP, and the RPE cell markers, RPE-9 and RPE-15, were not altered by any of the cytokines tested. Furthermore, IFN-gamma induced a striking enhancement of the expression of the photoreceptor cell protein, S-antigen. In contrast, IFN-alpha and TNF did not affect the expression of S-antigen. These studies show that the cytokine, IFN-gamma, can enhance a distinct cellular protein associated with cells committed to a specific cell lineage.

Antigens↗

[Chromosome abnormalities and tumor suppressor gene in childhood cancer].

Retinoblastoma gene has been cloned, and gene product has been characterized precisely. Recently, Wilms' tumor gene has been cloned, and interestingly, its expression was found in genitourinary system, suggesting that anomaly of this system was due to WT gene itself. Molecular analysis performed in colon cancer suggested that several tumor suppressor genes were involved in carcinogenesis and progression of this tumor. These findings revealed that tumor suppressor genes were involved in the development of adult cancer as well as childhood embryonal tumors. Chromosome abnormalities and tumor suppressor gene in childhood cancer are reviewed and referred to future prospects.

Child↗

[Formation of a stump after enucleation].

Despite the progress achieved in the treatment of ocular diseases, removal of the eyeball still has to be resorted to rather often. The records of 12 hospitals of Moscow over a year evidence 678 enucleations and eviscerations, 248 (39 percent) of these for oncologic diseases, 189 (29.1 percent) because of injury aftereffects, 153 (24 percent) because of glaucoma, and 58 (8 percent) because of ocular inflammations. Common enucleation was carried out in 203 of +/- 400 patients (except oncologic ones) and enucleation with implantation of biological and synthetic drafts in 197 cases, i.e. in half of the patients who needed it; this is explained by the absence of the necessary implants in hospitals. A bank of grafts should be created for centralized provision of ocular hospitals.

Adult↗

[Flow cytometry analysis of retinoblastoma and its clinical significance].

Flow cytometry (FCM) is a new technic that determines with precision the cellular DNA content and its distribution in various phases of the cell cycle. Using FCM, we analysed paraffin embedded tissue masses of retinoblastoma from 20 patients with the results that the rate of occurrence of DNA heteroploid was 35%; the occurrence rate of heteroploid in the glaucoma stage and the extraocular stage was higher than that in the intraocular stage (P less than 0.02); the postoperative survival rate of the diploid and near-diploid tumors was obviously higher than that of the heteroploid (P = 0.01); the cellular proportion in the G2M stage of the heteroploid and the index of cell proliferation was obviously higher than that of the diploid and near-diploid (P less than 0.05). This technique is of value in estimating the prognosis of retinoblastoma.

Aneuploidy↗

Abnormalities in structure and expression of the retinoblastoma gene in small cell lung cancer cell lines and xenografts in nude mice.

The putative retinoblastoma gene (Rb) is a tumor suppressor gene which is believed to cause retinoblastomas when both alleles are inactivated, leading to lack of the encoded Mr 110,000-116,000 phosphoprotein. Inactivation of the Rb gene has also been found in several other tumor types, including small cell lung cancer (SCLC). Absence of the 4.7 kilobase mRNA has been found to be frequent in SCLC, and it has been reported that the Rb Mr 110,000-116,000 protein product is always absent, even in tumors expressing Rb mRNA. Using Western blotting technique with a monoclonal antibody directed against the Rb protein, we investigated the expression of the Mr 110,000-116,000 Rb protein in SCLC tumors grown as xenografts in nude mice and/or as cell lines. Rb messenger RNA expression was determined by Northern blotting, and gross structural gene alterations were investigated by Southern blotting. Tumors established from 23 patients were studied. Seven of the tumors did not express Rb protein, whereas expression was detectable in 13. Three tumors were not investigated for protein expression. Only two tumors expressed Rb mRNA without detectable Rb protein expression. Gross DNA alterations were found in four tumors, of which only one expressed Rb mRNA. Our results demonstrated frequent absence of Rb mRNA and protein in SCLC, but apparently normal Rb mRNA and protein were both expressed in more than one-half of the tumors.

Animals↗

Ophthalmic neoplasms in infancy and childhood.

The most common ocular and orbital tumors presenting in infancy, childhood and adolescence are presented and discussed in this review. It has been prepared specifically for the clinical pediatrician and focuses on the clinical recognition of ophthalmic neoplasms, their diagnostic evaluation employing the use of advanced imaging techniques, biopsy when indicated and extent of disease workup. In addition, current treatment modalities are discussed. Ocular tumors addressed include: retinoblastoma, capillary hemangioma, lymphangioma, dermoid and epidermoid cysts, teratoma, glioma, astrocytic hamartoma, neurofibroma, rhabdomyosarcoma and fibrous tumors. Two aggressive and potentially fatal tumors, rhabdomyosarcoma and retinoblastoma, are presented in detail. In addition, the ocular tumors associated with the phakomatoses (von Hippel-Lindau, tuberous sclerosis and neurofibromatosis) are reviewed.

Adolescent↗

Vascular basophilia in ocular and orbital tumors.

The occurrence of vascular basophilia in ocular tumors has been a selective histologic feature of retinoblastomas. We recently observed a metastatic oat-cell carcinoma to the choroid which also demonstrated such a vascular hematoxyphilia. Histologic review of a variety of ocular and orbital metastatic carcinomas failed to yield a similar basophilic pattern. Examination of 100 consecutive retinoblastomas for vascular basophilia revealed an incidence of 6.0%. Similar material was not seen in any of 125 melanomas, including 10 with areas of necrosis. Histochemical studies showed the basophilic material to be DNA, and electron microscopy revealed the nuclear debris of pyknotic tumor cells to be continuous with identical material surrounding the adjacent blood vessels. The pathogenesis of vascular deposition of DNA in these two ocular tumors remains unclear. This finding most likely represents a form of tumor activity requiring comparatively healthy blood vessels to adequately precipitate liberated nucleic acids being filtered from the necrotic and degenerating tumor tissue.

Basophils↗

[Aqueous humor].

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Acetazolamide↗

[Suppressor genes in the malignant transformation and genic deletions in human cancers].

Experimental studies of cell malignant transformation have shown that such transformation requires the alteration of genes that can control the expression of the transformed phenotype. In human oncology, the role of genes that suppress malignant transformation is suggested by the fact that specific genic deletions have been detected by polymorphism-detecting probes in many malignant tumours. The only oncosuppressor gene that is characterized at the moment is the inactivated RB gene in retinoblastoma. Molecular biology studies have shown that in retinoblastoma and other malignant tumours this gene is altered in its structure or expression. In addition to retinoblastoma, nephroblastoma in children and colonic carcinoma constitute models for the study of oncosuppressor genes in human oncology.

Cell Transformation, Neoplastic↗

[Construction technic for globular and palpebral ocular prosthesis].

A prosthesis mounted on dark glasses was made for the right eyeball and lid of, a child of 13, one year after exeresis and chemotherapy following a recurring liposarcoma. The presence of local or distant metastases was ruled out. The aestheti improvement reduing socila disomfort is clearly illustrated in photographs taken before (1) and after (8).

Adolescent↗