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At least 325 records · Page 18Linked to original sources
PubMed1987

Structural evidence for the authenticity of the human retinoblastoma gene.

The retinoblastoma (Rb) gene is the prototype for a class of recessive human cancer genes in which loss of activity of both normal alleles is thought to be associated with tumorigenesis. Sixteen of 40 retinoblastomas examined with a complementary DNA probe shown to be the Rb gene had identifiable structural changes of the Rb gene including in some cases homozygous internal deletions with corresponding truncated transcripts. An osteosarcoma also had a homozygous internal deletion with a truncated transcript. In addition, possible hot spots for deletion were identified within the Rb genomic locus. Among those tumors with no identifiable structural changes there was either absence of an Rb transcript or abnormal expression of the Rb transcript. Comparison of the structural changes in the tumor cells and fibroblasts of certain patients provided support for Knudson's two-hit hypothesis for the development of retinoblastoma at the molecular level. The ability to detect germline structural deletions in fibroblasts from some patients with bilateral retinoblastoma also indicates that the isolated gene is useful for diagnostic purposes.

Alleles↗
PubMed1984

Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage.

A domain of DNA designated N-myc is amplified 20- to 140-fold in human neuroblastoma cell lines but not in cell lines from other tumor types. N-myc has now been found to be amplified in neuroblastoma tissue from 24 of 63 untreated patients (38 percent). The extent of amplification appears to be bimodal, with amplification of 100- to 300-fold in 12 cases and 3- to 10-fold in 10 others. Amplification was found in 0 of 15 patients with stage 1 or 2 disease, whereas 24 of 48 cases (50 percent) with stage 3 or 4 had evidence of N-myc amplification. These data indicate that N-myc amplification is a common event in untreated human neuroblastomas. Furthermore, N-myc amplification is highly correlated with advanced stages of disease (P less than 0.001) and with the ability to grow in vitro as an established cell line, both of which are associated with a poor prognosis.

Adolescent↗
PubMed1979

Primary cutaneous malignant melanoma metastatic to the iris.

We describe a case of cutaneous malignant melanoma metastatic to the iris as the first presenting sign of metastases 10 years after excision of the primary tumour. The histology of the excised iris metastases and the primary skin melanoma are compared. Progressive intracranial metastatic growth did not correlate with the observed regression of the residual intraocular melanoma cells during cyclical cytotoxic therapy.

Adult↗
PubMed1981

Ocular malignant melanoma in South African blacks.

The incidence of primary ocular malignant melanoma in blacks during the last 25 years in a large part of the Transvaal Province of South Africa is reported. Only 8 cases were diagnosed, 1 uveal, 4 conjunctival, and 3 orbital. During this same period 153 cases of primary ocular malignant melanoma were diagnosed in whites. The rarity of these tumours among blacks is stressed and the reasons for this infrequent incidence discussed.

Adult↗
PubMed1985

Physiological and pathobiological significance of ocular glycoproteins. I. Studies using fluorescein labelled glycine max.

Cell surface carbohydrates play an important role in several biological, immunological, and neoplastic phenomena including development, growth regulation, cellular locomotion, receptor activation, and tumour metastasis. Fluorescein labelled lectins which bind to specific carbohydrate residues in glycoproteins and glycolipids are being increasingly used as chemical probes to study cell components. Several different preparations of ocular tissues from human, rabbit, and rat were examined for the distribution of N-acetyl-D-galactosamine (D-gal NAc) by means of fluorescein-labelled lectin from soybean (glycine max). A very strong fluorescence was observed in the corneal epithelium; Descemet's membrane and corneal endothelium were also strongly fluorescent. The conjunctival epithelium similarly showed a strong reaction, as did the goblet cells. The iris epithelium and the dilator pupillae were only weakly fluorescent, but the ciliary body showed strong fluorescence, as did the blood vessels. As compared with lens fibres the lens epithelium was strongly fluorescent. The outer retina, that is, the photoreceptors, the pigment epithelium, and Bruch's membrane, showed a very strong reactivity. The optic nerve showed moderate fluorescence, but reaction with extraocular muscles was variable. The skin of the upper and lower eyelids, hair follicles, and blood vessels showed strong lectin binding. Sections of retinoblastoma and malignant melanoma showed no reaction. The physiological and pathological significance of these findings is discussed.

Acetylgalactosamine↗
PubMed1985

Assessment of immunological techniques in the diagnosis and prognosis of ocular malignant melanoma.

Tests of cell mediated immunity (one and two stage leucocyte migration inhibition assays) and humoural immunity (membrane immunofluorescence and serum effects on leucocyte migration) were done with leucocytes and sera from 36 patients with uveal melanoma, five with conjunctival melanoma, 21 with non-malignant ocular disease, and 189 with cutaneous melanoma. Cell mediated reactivity with melanoma extracts and serum reactivity with cultured melanoma cells were significantly more frequent in the melanoma patients, but control donor reactivity was also relatively high. Maximum reactivity was found with cells or serum from those patients in whom, on pathological examination, the intraocular melanoma had penetrated the sclera and in patients with conjunctival melanoma. Maximum separation of melanoma patients from control donors was achieved by consideration of the results of several tests done simultaneously. These immunopathological studies were made during the period from 1972 to 1978. At follow-up in 1983 four of the five patients suffering from conjunctival melanoma had died from metastases, and 10 of the 36 with uveal melanoma had died from metastatic disease. The immunological reactions, while of some value in separating melanoma patients from those without melanoma, did not predict whether a particular patient with uveal melanoma would die of metastatic disease or would survive.

Antibody Formation↗
PubMed1987

Characterisation of ocular melanoma with cutaneous melanoma antibodies.

It can be difficult to distinguish between various forms of pale intraocular tumour, and in particular between an amelanotic malignant melanoma, a choroidal haemangioma, and a solitary metastasis. If a monoclonal antibody specific for melanoma could be identified, it might be radiolabelled to provide a scanning technique which could distinguish between an ocular melanoma and a similar lesion. This pilot, in vitro study was undertaken to determine if monoclonal antibody against cutaneous melanoma recognises any antigenic similarity in ocular melanomas. Three cutaneous melanoma MoAbs 225.28S, 376.96S, and 763-24T and a non-specific MoAb HMFG2 were studied. Cell impressions were obtained from fresh ocular malignant melanomas. Standard staining techniques with immunofluorescence were used. MoAb 225.28S, 376.96S, and 763.24T were positive in melanomas with a dominant epithelioid cell type and in those with a dominant spindle cell type. It is concluded that MoAb 225.28S, 376.96S, and 763.24T may be suitable for imaging ocular melanomas after labelling with 123I, 111In, or 99mTc.

Antibodies, Monoclonal↗
PubMed1993

Analysis of the incidence of intraocular metastasis.

The incidence of metastases to the uvea is compared with that in eight other (extraocular) target sites, in patients with metastatic primary carcinomas of the breast, colorectum, and lungs. The incidence of intraocular metastases from breast cancer is lower than in the eight other target organs surveyed; in the other primary cancers, the incidences were midway between those in the other sites, However, when the incidence of intraocular metastases is viewed in relation to the calculated numbers of cancer cells delivered via the arterial route, the uveal tract is the most highly favoured target site for the development of metastases per unit of delivered cancer cells.

Breast Neoplasms↗
PubMed1996

Multidrug resistance in ocular melanoma.

AIMS/BACKGROUND: Metastatic disease in patients with ocular melanoma is resistant to chemotherapy. One of the main mechanisms of modulating multidrug resistance is the expression of the multidrug resistance gene 1 (MDR1) product (p-glycoprotein) by tumour cells. The purpose of this study was to evaluate the frequency of expression of the MDR1 gene in ocular melanoma whose primary treatment was surgical excision or enucleation. METHODS: Twelve recent ocular melanomas were received fresh, snap frozen and cryostat sections of tumour were analysed for expression of MDR1 by immunohistochemistry using a well characterised monoclonal antibody to MDR1. Tumour explants were established in short term tissue culture from four tumours and cell blocks were examined by immunohistochemistry. RESULTS: MDR1 expression was present in five of 12 ocular melanomas. Upregulation of protein expression was found in four cell lines established in short term culture from tumour explants. A recurrent tumour, initially treated by local excision and radioactive plaque, showed overexpression of MDR1 mRNA. CONCLUSIONS: These results suggest that significant level of MDR1 may be intrinsically present in ocular melanomas before exposure to drugs involved in multidrug resistance, and indicate the possible importance of MDR1 in modulating chemoresistance in ocular melanoma. Chemosensitisation may be of potential value in planning adjuvant chemotherapy for patients with metastatic disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1988

Application of linkage analysis to genetic counselling in families with hereditary retinoblastoma.

Six families with retinoblastoma in more than one member were investigated with DNA markers linked to the retinoblastoma locus because direct analysis had not disclosed the gene defect. In all of the families we could identify the affected chromosome and predict the genetic risk with a high level of confidence (90 to 99%). In one patient the test helped to detect tumour development earlier than usually possible. Several subjects were found not to carry a mutation, thus obviating frequent ophthalmological examinations under anaesthesia as would be necessary otherwise. These results show that linkage analysis can be successfully applied to genetic counselling in families with hereditary retinoblastoma.

Adult↗
PubMed1991

Application of PCR amplification of DNA from paraffin embedded tissue sections to linkage analysis in familial retinoblastoma.

A family segregating for the retinoblastoma predisposition gene has been analysed using the polymerase chain reaction to exclude their son as being an affected gene carrier. The unusual feature of this family is that the affected child, who would ordinarily have been used to establish phase in a linkage study, died as a result of developing a second tumour some years ago. The only tissue available from this child was a paraffin embedded, formalin fixed histopathological specimen from the second tumour. It was possible to isolate DNA from this tissue and amplify the DNA flanking two polymorphic restriction enzyme sites to establish alleles which cosegregated with tumour predisposition. Archival material can now be used to offer families such as this prenatal screening to provide informed genetic counselling.

Base Sequence↗