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At least 469 records · Page 26Linked to original sources
PubMed1997

In vitro efficacy of carboplatin and hyperthermia in a murine retinoblastoma cell line.

PURPOSE: To determine the cell-killing activity of varying doses of carboplatin, graded hyperthermia, and the combination of carboplatin and hyperthermia in the treatment of a transgenic murine retinoblastoma cell line. METHODS: Replicate cell wells (more than six wells per dose point) from an established transgenic murine retinoblastoma cell line (Rb-6) were exposed to a single application of hyperthermia for 15, 30, 60, and 120 minutes at temperatures of 37 degrees C (control), 40 degrees C, and 43 degrees C. Carboplatin dose response treatment was studied at doses of 2000, 1000, 500, 400, 300, 200, 100, and 50 ng per well. Combined treatment studies used these carboplatin dosages with each of the graded hyperthermia exposure temperatures at each exposure time. At 24 hours, all wells were pulsed with 3H-thymidine for 24 hours, washed three times, harvested, and counted. Raw counts (3H-thymidine) were fitted to a linear regression model to calculate the lethal dose for 50% (LD50) of cells. RESULTS: The LD50 for carboplatin exposure at 37 degrees C occurred at 542 ng. The LD50 for hyperthermia at 40 degrees C occurred at 90 minutes and at 43 degrees C it occurred at 62 minutes. Combined hyperthermia and carboplatin exposure yielded a synergistic interaction with an LD50 of 327 ng at 43 degrees C for 30 minutes. Determination of a thermal enhancement ratio yielded an enhancement range of 1.1 to 25.8. CONCLUSIONS: The synergistic cytocidal interaction of heat and carboplatin in a transgenic murine retinoblastoma cell line has been established in this study. The increased thermal enhancement ratio documents the potential utility of combined treatment applications in reducing treatment levels of single-modality therapy, potentially allowing for a decrease in treatment-related morbidity.

Animals↗
PubMed1998

Diffuse ocular metastases as an initial sign of metastatic lung cancer.

A 68-year-old man with lung carcinoma and no systemic metastasis presented with a blind, painful right eye. Examination showed no perception of light in the affected eye, elevated intraocular pressure, marked epibulbar hyperemia, and a white placoid mass in the conjunctiva nasally. Although a cataract precluded a clear view of the fundus, ultrasonography disclosed a total retinal detachment and a diffuse thickening of the choroid. Metastatic carcinoma was suspected clinically and the eye was enucleated because of severe, intractable pain. Pathologic examination demonstrated extensively necrotic metastatic adenocarcinoma involving the conjunctiva, peripheral cornea, sclera, iris, ciliary body, choroid, optic nerve, subarachnoid space, and orbit. Metastatic disease usually affects a singular ocular tissue, and it is highly unusual for such widespread ocular involvement to be the first sign of systemic metastasis from a primary neoplasm.

Adenocarcinoma↗
PubMed1997

Cerebral primitive neuro-ectodermal tumour following treatment of a unilateral retinoblastoma.

Cerebral primitive neuro-ectodermal tumour (PNET) occurring as a second primary malignancy in childhood is exceedingly rare. We present a 7-year-old boy who developed a proven supratentorial PNET five years after enucleation and radio-/chemotherapy for a sporadic, unilateral retinoblastoma with optic nerve invasion. The association with this malignant eye disease as well as the effect of irradiation and multi-agent chemotherapy on second tumour induction are evaluated.

Chemotherapy, Adjuvant↗
PubMed1998

Vincristine- and cisplatin-induced apoptosis in human retinoblastoma. Potentiation by sodium butyrate.

Chemotherapy alone has largely been unsuccessful in controlling retinoblastoma growth, and has traditionally been limited in use as an alternative to irradiation for the treatment of retinoblastoma. Recently, clinical studies combining chemotherapy with local therapies, including radiotherapy, laser therapy or cryotherapy and in some cases, cyclosporine A, have been effective in treating retinoblastoma. Differentiating agents may also be combined with chemotherapy to enhance the action of cytotoxic drugs on tumor cell growth, although this approach has not been fully investigated in retinoblastoma. In this study, we evaluated the cytotoxic response of human retinoblastoma cell lines (Y79 and WERI-Rb1) to two chemotherapy agents commonly used in treating retinoblastoma, vincristine (VCR) and cisplatin (CDDP). Retinoblastoma cells have been shown to be sensitive to the differentiating agent sodium butyrate, and cell lines were also treated with a combination of VCR or CDDP with sodium butyrate, and the effects on retinoblastoma viability assessed. Both VCR and CDDP induced dose-dependent death of Y79 and WERI-Rb1 cells, accompanied by nuclear and cytoplasmic condensation and DNA laddering, features characteristic of apoptosis. Inhibitors of macromolecular synthesis, cycloheximide and actinomycin-D, significantly reduced VCR- and CDDP-induced apoptosis, although putative endonuclease inhibitors zinc sulphate and aurintricarboxylic acid had no apparent effect. Treatment with 0.5 mM or 1 mM sodium butyrate combined with VCR or CDDP significantly increased induction of apoptosis by these agents. This augmentation of chemotherapy-induced apoptosis may have implications for retinoblastoma therapy.

Antineoplastic Agents↗
PubMed2003

Comparative genomic hybridisation divides retinoblastomas into a high and a low level chromosomal instability group.

BACKGROUND: Retinoblastoma is the most common intraocular malignancy in childhood and is responsible for approximately 1% of all deaths caused by childhood cancer. AIMS/METHODS: Comparative genomic hybridisation was performed on 13 consecutive, histologically confirmed retinoblastomas to analyse patterns of chromosomal changes and correlate these to clinicopathological variables. Six cases were hereditary and seven cases were sporadic. RESULTS: In 11 of the 13 tumours chromosomal abnormalities were detected, most frequently gains. Frequent chromosomal gains concerned 6p (46%), 1q (38%), 2p, 9q (30%), 5p, 7q, 10q, 17q, and 20q (23%). Frequent losses occurred at Xq (46%), 13q14, 16q, and 4q (23%). High level copy number gains were found at 5p15 and 6p11-12. A loss at 13q14 occurred in three cases only. Relatively few events occurred in the hereditary cases (27) compared with the non-hereditary cases (70 events). The number of chromosomal aberrations in these 13 retinoblastomas showed a bimodal distribution. Seven tumours showed less than four chromosomal aberrations, falling into a low level chromosomal instability (CIN) group, and six tumours showed at least eight aberrations, falling into a high level CIN group. In the low level CIN group the mean age was half that seen in the high level CIN group, there were less male patients, and there were more hereditary and bilateral cases. Microsatellite instability was not detected in either of the two groups. CONCLUSION: Despite the complex pattern of genetic changes in retinoblastomas, certain chromosomal regions appear to be affected preferentially. On the basis of the number of genetic events, retinoblastomas can be divided in low and a high level chromosomal instability groups, which have striking differences in clinical presentation.

Age Factors↗
PubMed2005

Murine model of primary intraocular lymphoma.

PURPOSE: Primary intraocular lymphoma (PIOL) is a subtype of central nervous system lymphoma. Although this lymphoma is rare, its incidence has tripled in the past 15 years. Currently, the only available model is a murine metastatic malignant lymphoma that occurs after intraperitoneal inoculation of Rev-2-T-6 lymphoma cells into newborn syngeneic mice. The current study was conducted to develop a new experimental model for PIOL. METHODS: Rev-2-T-6 cells (0.5 x 10(5) or 1.0 x 10(5)) were inoculated into the vitreous of adult BALB/c mice. Mice were monitored clinically every other day and under fundoscopic examination weekly. They were euthanatized on weeks 3, 5, 6, 7, or 8, after inoculation. All eyes were processed for histology. Immunohistochemistry was performed with an antibody (p14) specific for Rev-2-T-6 cells. Cytokine mRNA expression (IL-2, -4, -6, -10, and IFN-gamma and CC chemokine receptor-1 [CCR1]) was assayed in the lymphoma cells by microdissection and RT-PCR. IL-10 and -6 levels in the vitreous were measured by ELISA. RESULTS: Within 2 to 4 weeks, tumor cells from the vitreous migrate through the retina and gather between the RPE cell and retina. Rarely (>2 months after inoculation), Rev-2-T-6 cells may break through the RPE and infiltrate the choroid and sclera. Tumor localization was confirmed by immunohistochemistry. The intraocular lymphoma cells produce high levels of IL-10, IFN-gamma, and CCR1 transcripts. A high level of IL-10 was detected in the vitreous inoculated with Rev-2-T-6 cells. CONCLUSIONS: The data suggest that RPE cells constitute a barrier to the spread of intraocular lymphoma. Intravitreal injection of Rev-2-T-6 cells is a novel model of PIOL in immune-competent hosts that will aid in understanding the molecular mechanisms of the disease.

Animals↗
PubMed1999

Trilateral retinoblastoma: a meta-analysis of hereditary retinoblastoma associated with primary ectopic intracranial retinoblastoma.

PURPOSE: To obtain refined knowledge regarding trilateral retinoblastoma (TRb), which is a syndrome that consists of hereditary retinoblastoma associated with an intracranial neuroblastic tumor. MATERIALS AND METHODS: Using a systematic literature review, we contacted authors to obtain missing information. Data from 106 children were used in a meta-analysis including frequency distributions and Kaplan-Meier survival curves. RESULTS: TRb showed no sex predilection. Median age at diagnosis of retinoblastoma was 5 months (range, 0 to 29 months); age at diagnosis was younger among 47 children (47%) with familial retinoblastoma compared with age at diagnosis among 52 children (53%) with sporadic retinoblastoma (2 v 6.5 months, P <.0001). TRb usually affected the second or third generation with retinoblastoma. Median time from retinoblastoma to TRb was 21 months (range, 6 months before to 141 months after); time to TRb was longer for 78 (77%) pineal tumors compared with 23 (23%) suprasellar tumors (32 v 6.5 months, P <.0001). The size (27 v 32 mm, P =.57) and prognosis (survival of 9 v 8 months, P =.91) of pineal and suprasellar tumors were similar. TRb was detected earlier (1 v 22 months, P =.0007) and the child survived longer if neuroimaging was routinely performed (16 v 8 months, P =.001), but age at death was similar (36 v 37 months, P =.98). Cumulative 5-year survival (which was likely to indicate cure) was 27% (v 0%) if screening was undertaken. All children whose TRb exceeded 15 mm in size died. CONCLUSION: The family history, age at diagnosis, and laterality of retinoblastoma in children with TRb resembled that of ordinary hereditary retinoblastoma. Suprasellar TRb were diagnosed earlier, and may arise earlier, than pineal TRb. Screening by neuroimaging could improve the cure rate if cases of TRb were detected when tumors were 15 mm or smaller in size.

Age of Onset↗
PubMed1997

[The relationship between the prognosis of retinoblastoma and proliferating cell nuclear antigen and argyrophilic protein at nucleolus organizer regions].

OBJECTIVE: To investigate the relationship between the proliferative activity of retinoblastoma (Rb) cells and the prognosis of the tumor. METHODS: Proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizer regions (AgNORs) in paraffin-embedded Rb specimens from 48 cases were detected by LSAB immunohistochemical method using an anti-PCNA monoclonal antibody and the technique of ploton. RESULTS: The PCNA labeling index (PCNALI) and the AgNORs counts were well correlated (r = 0.647, P < 0.001). In 29 patients of the 48 cases receiving simple eyeball extirpation and being followed up for 5 years, the mean PCNALI and the mean numbers of AgNORs per nucleus in 19 patients surviving > or = 5 years after operation were markedly lower than that in 10 patients surviving < 5 years after operation (P < 0.01, P < 0.05). CONCLUSION: It is indicated that the PCNALI or the AgNOR count is negatively related with the clinical prognosis of Rb patients, and can be useful in judging the prognosis.

Eye Enucleation↗
PubMed1998

[Insufficient understanding of second tumors after childhood neoplasms in Switzerland].

Second malignancy after childhood neoplasms is a well-known complication. However, frequency differs considerably according to the types of primary neoplasm and the specifics of therapy. Ten patients with a second malignancy after being cured of the primary tumor are described. There were 2 patients with acute lymphoblastic leukemia, one with non-Hodgkin's lymphoma, and one with breast cancer after Hodgkin's disease. Two patients with heritable retinoblastoma developed osteosarcomas in the irradiation field after a latent period of 7 and 14 years respectively. There was another osteosarcoma in a Wilms' tumor survivor. One patient with acute lymphoblastic leukemia developed a secondary AML 10 years after achieving initial remission, and a meningioma was diagnosed in another patient with cured acute lymphoblastic leukemia. One patient died of peritoneal sarcomatosis of unknown origin 20 years after the diagnosis of acute myeloid leukemia. All patients received radiotherapy for the primary neoplasms. Secondary neoplasms in other patients were probably missed because they occurred in adulthood when the patients were transferred to other medical centres. It is impossible to trace these patients because central registration of patients with neoplasms is lacking. It is therefore important to establish a central cancer registry for the whole of Switzerland. Second malignancy after childhood cancer is not a rare event and requires long-term follow-up of patients with neoplasms.

Adolescent↗
PubMed2004

Incidence of eye cancer in Taiwan: an 18-year review.

PURPOSE: To describe the incidence and histologic patterns of eye cancers in Chinese in Taiwan. METHODS: Beginning in 1979, cases of cancer in Taiwan were reported to the Taiwan National Cancer Registry. Information on all Chinese patients diagnosed with eye malignancies under the International Classification of Disease, Ninth Revision, site 190, was retrieved for analysis from the data bank of the Taiwan National Cancer Registry. RESULTS: In all, 733 cases with primary eye cancers were identified from 1979 to 1996, an 18-year period. The average annual age-standardized incidence of eye cancers was 2.46 per million population (2.57 for male and 2.33 for female). For cases less than 15 years of age, the most common eye malignancy was retinoblastoma (86.0%), followed by rhabdomyosarcoma (3.9%) and lymphoma (2.8%). For cases 15 years of age or older, the most common eye malignancy was melanoma (28.6%), followed by squamous cell sarcoma (21.0%) and lymphoma (20.8%). CONCLUSIONS: The time trends of the incidence of eye cancers were relatively stable over the 18-year period in Taiwan. Retinobalstoma, melanoma, and lymphoma were the three most common eye cancers in this Chinese population.

Adolescent↗
PubMed2004

Role of skeletal scintigraphy in advanced retinoblastomas.

PURPOSE: To document the incidence of skeletal metastases exclusively in advanced cases of retinoblastoma and to rationalize the use of preoperative skeletal scintigraphy in such patients. MATERIAL AND METHODS: Preoperative bone scans of 36 consecutive patients with advanced retinoblastoma who underwent skeletal scintigraphy during 1998 to 2003 were analyzed retrospectively. Bone scans were classified as: Grade 1 (high probability scan for skeletal metastases), Grade 2 (equivocal malignant or benign abnormalities), or Grade 3 (normal or certainly benign lesions). RESULTS: Grade 1 scan was found in 3 (8.33%) patients; bone metastases were confirmed by additional investigations. Grade 2 scan was found in 5 (13.88%) patients; bone metastases were excluded in all by additional investigations. Grade 3 scan was found in the remaining 28 (77.77%) patients. Extraorbital extension of disease was demonstrated by fine needle aspiration of lymph nodes in five patients, which included all three patients with Grade 1 scan. In addition to lymph node metastases, two patients had intracranial extension of the disease; demonstrated by contrast-enhanced magnetic resonance imaging of the head. One patient had liver metastases detected on abdominal ultrasound. None of the patients had skeletal metastases only. CONCLUSION: Routine preoperative bone scan is not justified in patients with locally advanced retinoblastoma. Bone scan should only be performed in patients with documented extraocular metastatic disease.

Adolescent↗
PubMedDate not supplied

Detection of mutations in argentine retinoblastoma patients by segregation of polymorphisms, exon analysis and cytogenetic test.

The aim of this study was to detect chromosomal and molecular abnormalities in 16 Argentine families with retinoblastoma (RB). Chromosomes were analyzed by G-banding, DNA from leukocytes and tumors was studied by segregation of polymorphisms within RB gene (RB1) and the DNA from chorionic villus by sequencing. The karyotype of an Rb236 bilateral patient with dismorphic signs revealed a deletion in 13q13-21. Polymorphism and exon analyses showed a deletion in the 3' end of RB1 in an Rb72 patient. The mutant RB1 allele, detected by loss of heterozygosity (LOH) in the tumor, was identified in 14 out of 18 tumors. The analysis of chorionic villus revealed a mutation, a C-to-T transition in exon 18. Molecular and cytogenetic analyses in families with RB offer valuable information on how to assess the risk of tumor development.

Argentina↗
PubMed2002

[Eye complaints indicative of a tumor elsewhere in the body].

A variety of clinical presentations of malignant tumour metastases outside of the eye and orbit, were seen in four patients: a 52-year-old man who was scheduled to have a surgical removal of an oesophageal carcinoma and who presented with retinal detachment, a 58-year-old woman in whom retinopathy was the first sign of a cervical carcinoma (cancer-associated retinopathy), a 71-year-old man who had been treated for colon carcinoma and who presented with an orbital mass, and finally a 67-year-old woman with an orbital mass as the first sign of a Grawitz tumour. Metastasis should be considered in patients with a history of malignancy, who present with ophthalmologic complaints. Further it should be borne in mind that eye problems can be the first sign of oncological disease outside the eye.

Aged↗