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Biomedical subjects

S Neuenschwander

Publications and source records attributed to S Neuenschwander.

At least 73 records · Page 4Linked to original sources

Etoposide and carboplatin in extraocular retinoblastoma: a study by the Société Française d'Oncologie Pédiatrique.

PURPOSE: A phase II study of etoposide (VP-16) and carboplatin was performed in patients with extraocular retinoblastoma to evaluate the response rate with this drug combination. PATIENTS AND METHODS: Twenty patients with extraocular retinoblastoma, age 9 to 120 months, were included in a cooperative multicenter phase II study of the Société Francçaise d'Oncologie Pédiatrique (SFOP). The schedule consisted of consecutive 5-day treatment with VP-16 100 mg/m2/d and carboplatin 160 mg/m2/d. RESULTS: The response rate for the 20 patients was 85%; there were nine complete responses and eight partial responses. Hematologic toxicity was the only serious observed toxicity and was always manageable. CONCLUSION: This combination of VP-16 and carboplatin is highly effective in extraocular retinoblastoma. The high response rate is encouraging for further evaluation of this drug combination in adjuvant chemotherapy when necessary after enucleation or in neoadjuvant chemotherapy for intraocular tumors.

Antineoplastic Combined Chemotherapy Protocols↗

Growth inhibition of MCF-7 breast cancer cells by stable expression of an insulin-like growth factor I receptor antisense ribonucleic acid.

Insulin-like growth factors (IGFs) play an important role in cellular proliferation, and IGF action appears to be involved in tumorigenesis. To determine the role of the IGF-I receptor in breast cancer cell growth, we stably transfected MCF-7 breast cancer cells with a construct encoding an antisense RNA complementary to the region surrounding the translation initiation site of the IGF-I receptor messenger RNA (mRNA). Control cells were transfected with vector alone. Clones expressing the antisense RNA exhibited a 30% reduction in endogenous IGF-I receptor mRNA levels and a significant reduction in receptor protein levels, as measured by both ligand binding assays and Western blot analysis. Antisense-expressing clones expressed approximately 30,000 receptors/cell compared with approximately 48,000-58,000 receptors/cell in control (neo) cells (P < 0.05). Although endogenous RNA:RNA hybrids were demonstrable in antisense-expressing cells, our results suggest that the major effect of the antisense may be the reduction in mRNA levels and not via an inhibition of translation. The reduction in receptor expression reduced both IGF-I- and serum-stimulated cellular proliferation. The maximum cell number reached at 96 h in the presence of IGF-I (100 ng/ml) was significantly reduced in antisense-expressing clones (22,000-30,000) compared with that in control (neo) cells (39,000-42,000). Furthermore, IGF-I-induced c-fos gene expression was reduced by 30% in the clones expressing the antisense RNA. These results strongly support a role for the IGF-I receptor in the proliferation of human breast cancer cells and suggest that strategies using this type of technology may prove useful in cancer therapy.

Breast Neoplasms↗

[Diagnosis of non-palpable breast lesions: contribution of cytological punctures after stereotaxic localization].

The authors reviewed the accuracy of stereotaxic fine-needle aspiration cytology. Two hundred-twenty-eight lesions were studied: 103 benign lesions, 125 cancers. Inadequate sample was obtained in 26% of cases. None of the cytology reports were false-positive, whereas 77% of the suspect cytologic reports were malignant on histology. In strongly suspicious lesions at mammography, the decision to perform surgical biopsy should not be postponed as false negative cytologic findings (7 cases) are possible. In patients with a low suspicious lesion, cytology found six cancers. The benign-to-malignant ratio of excisional biopsies of non palpables lesions should be reduced by stereotaxic fine-needle aspiration cytology.

Adult↗

The role of chemotherapy in orbital involvement of retinoblastoma. The experience of a single institution with 33 patients.

BACKGROUND: Orbital involvement is a rare occurrence in retinoblastoma but still carries a bad prognosis. The aim of this study was to define more clearly the role of chemotherapy in this advanced disease. METHODS: Between 1977 and 1991, 33 patients were treated at the Services de Pédiatrie at Institut Curie (Paris, France) for orbital involvement of retinoblastoma, which was isolated in 20 patients and associated with metastases in 13 patients (outside the central nervous system [CNS], 6; within the CNS, 7). Treatment included chemotherapy for 33 patients, irradiation of the orbit for 23 patients, and intrathecal chemotherapy and/or CNS irradiation in selected patients. RESULTS: The plateau phase of the survival curve was reached at 15 months, with a survival of 34% plus or minus 8%. The disease free interval was longer when patients had no CNS disease (P < 0.05). Twenty of the 21 recurrences (95%) occurred within 1 year after diagnosis of orbital involvement. CONCLUSIONS: Intensive chemotherapy using cyclophosphamide, platinum compounds, epipodophyllotoxins, doxorubicin, and vincristine was effective in orbital involvement of retinoblastoma even with associated extra-CNS metastases. However, associated CNS disease still carries a bad prognosis, and long term follow-up is necessary to evaluate the risk of a second tumor.

Antineoplastic Combined Chemotherapy Protocols↗

Identification and visuotopic organization of areas PO and POd in Cebus monkey.

Two visual areas of the anterior bank of the parietooccipital sulcus, areas PO and POd, were identified and their visual field representations were studied in six anesthetized and paralyzed Cebus monkeys. The definition of these areas was based on electrophysiological mapping and myeloarchitecture. PO is located in the ventral aspect of the anterior bank of the parietooccipital sulcus and ventral precuneate gyrus. It borders area V2 posteriorly and ventrally in the depth of the parietooccipital sulcus, area V3d laterally, and another undescribed visual area medially. POd was located dorsal to area PO and ventral to architectonic area PE. The representations of the visual field in areas PO and POd are complex. In each hemisphere, these areas have a virtually complete representation of the contralateral visual hemifield. Different from the previously described visual areas, in PO and POd there is a precise organization of isopolar lines and a complex organization of the isoeccentric ones. In PO, as well as in POd, the representation of the horizontal meridian runs dorsoventrally along the parietooccipital sulcus. The upper visual quadrant is represented medially and the lower visual quadrant laterally. A large and complex representation of the periphery, from 20 degrees to 60 degrees eccentricity is present at the lateral and medial portions of these areas. By contrast, the representation of the central 20 degrees is very small in both PO and POd. The central visual field is represented ventrally in PO and dorsally in area POd. Area POd shows a more stratified myeloarchitectonic pattern than PO and both areas can be distinguished from other surrounding areas by their heavier myelinated pattern.

Animals↗

Periosteal Ewing sarcoma.

PURPOSE: To evaluate the imaging and histopathologic findings and clinical course of patients with periosteal Ewing sarcoma (PES). MATERIALS AND METHODS: Conventional radiographs, computed tomographic (CT) scans, and magnetic resonance (MR) images in 10 adolescents and one adult were evaluated for the extent and character of PES. RESULTS: Ten of 11 masses were in the proximal extremities and one in the fibula; nine were diaphyseal and two, metadiaphyseal. Radiographs and CT scans showed a subperiosteal mass that did not invade the medullary cavity, was contiguous with and elevated the periosteum, and produced a Codman triangle and periosteal reaction. No PES exhibited osseous or cartilaginous matrix calcifications. MR imaging and histopathologic examination helped confirm the sparing of cancellous bone and the subperiosteal location. CONCLUSION: PES differs from the more common medullary and soft-tissue Ewing sarcomas in location, marked male predominance, and lack of presenting metastases. Except for the absence of matrix calcifications, PES resembles other periosteal sarcomas in imaging characteristics and a less aggressive clinical course.

Adolescent↗

Visually triggered neuronal oscillations in the pigeon: an autocorrelation study of tectal activity.

In this study we describe visually triggered gamma oscillations in the optic tectum of awake pigeons. This study was motivated by the potential relevance of synchronous oscillatory responses in perceptual binding in a laminated structure other than the mammalian neocortex. Tectal responses were recorded as local field potential and multiunit activity by differential filtering. The local field potential was analysed by computing its autocorrelation function and spectral power with a moving window applied to single response sweeps. The temporal structure of the spike trains was evaluated by computing averaged autocorrelograms. A damped sine wave function was fitted to the autocorrelograms in order to quantify the degree of oscillation of both signals. Epochs of significant oscillatory activity were observed in the local field potential in 60% of the trials (n = 39). In all trials, significant oscillations occupied approximately 10% of the time the stimulus was present. The oscillatory events in both the local field potential and the multiunit activity had frequencies in the range of 20-50 Hz. It is important to emphasize the great variability in the frequency and in the probability of occurrence of the oscillatory responses from trial to trial, which makes the oscillatory behaviour of the tectal activity highly non-stationary. The oscillatory activity we describe in the avian tectum has characteristics similar to those reported in the mammalian neocortex. These findings from a fully awake animal strengthen the universality of oscillations as a possible carrier for synchronization of activity in the constitution of neuronal assemblies.

Action Potentials↗

A dynamical analysis of oscillatory responses in the optic tectum.

Multi-unit recordings from the optic tectum of an awake pigeon displaying oscillatory behavior evoked by visual stimulus are highly non-stationary and contain a broad band of frequencies under a time-window analysis. Here we extend these observations by a non-linear dynamical analysis of these oscillatory signals (local fields potentials) in successive epochs during background activity and visual responses. Two numerical estimates have been obtained from the original data every 200 ms: (1) correlation dimension and (2) non-linear forecasting of the trajectories. Results from eight different recording sites analyzed are consistent and indicate, in the average, an increase in complexity of the signal during the oscillatory periods.

Animals↗

Distinct promoters in the rat insulin-like growth factor-I (IGF-I) gene are active in CHO cells.

In mammals, IGF-I mRNAs contain one of two different leader exon sequences that encode different 5'-untranslated regions (UTRs) and signal peptides. The pattern and regulation of expression of these exon 1 and exon 2-derived mRNAs suggests that the expression of each is controlled by a distinct regulatory region. In order to assess this possibility, DNA fragments consisting of sequences flanking and including the exon 1 and exon 2 transcription initiation sites were cloned into a luciferase expression vector and plasmid DNAs were transiently transfected into Chinese hamster ovary (CHO) cells. A fragment containing approximately 1.1 kb of sequence flanking the most upstream exon 1 transcription initiation site and 362 bp of exon 1 sequence did not stimulate luciferase activity. However, fragments containing 133 bp of 5'-flanking sequence and either 362 or 192 bp of exon 1 sequence stimulated luciferase activity significantly above that seen with a promoterless control plasmid. When the -133/+362 fragment was cloned in the opposite orientation with respect to the luciferase cDNA, the same level of promoter activity was observed. Removal of approximately 860 bp from the inactive fragment (i.e., approximately 782 bp of flanking sequence and approximately 74 bp of exon 1 sequence) resulted in promoter activity which was significantly greater than that seen with the promoterless luciferase expression vector, but which was less than that observed with fragments containing the proximal 133 bp of 5'-flanking sequence. Plasmids containing approximately 1.5 kb or 0.5 kb of flanking sequence and 44 bp of exon 2 sequence also significantly stimulated luciferase activity. These results constitute the first demonstration that both exon 1 and exon 2 transcription start sites are associated with distinct and potentially independently regulatable promoters and provide a molecular basis for the differential expression of these leader exons by developmental, tissue-specific and hormonal factors.

Animals↗

PCR assay for chromosome 1p deletion in small neuroblastoma samples.

Deletion of the short arm of chromosome 1 is among the most recurrent cytogenetic alterations found in neuroblastoma and has been associated with short survival. However, this prognostic information, which relies on time-consuming techniques, is not yet routinely exploited. In order to set up a reliable and simple routine test to determine 1p deletion in neuroblastoma, we have used the polymerase chain reaction to genotype neuroblastoma DNA at 2 loci containing a variable number of tandem repeats and located on the distal part of the short arm of chromosome 1. Agarose gel electrophoresis and ethidium bromide staining of the amplification products enable a simple determination of constitutional and tumor genotypes at these loci to be made. A total of 37 samples from 29 patients were studied with this technique. Loss of heterozygosity (LOH) could be identified in 8 cases. In each case the results obtained were in agreement with those achieved by the Southern procedure. This technique will be of particular interest in the pretherapeutic analysis of 1p deletions in small tumor samples obtained by fine-needle aspirates of the primary tumor. It should also enable retrospective studies from paraffin-embedded tumor fragments to be made and provide information for the analysis of tumor heterogeneity in neuroblastoma and in other tumors with 1p deletions.

Base Sequence↗

Mammographic features of 455 invasive lobular carcinomas.

Of 6,009 cases of breast cancer studied, 455 (7.6%) were invasive lobular carcinoma (ILC); 341 of these (75%) were pure ILC and 114 (25%) were ILC mixed with ductal forms. The mammographic features were compared with those of the 5,554 other breast carcinomas. Pure ILCs were less frequently round (1% vs 11%) and more frequently spicular (28% vs 23%) or with architectural distortion (18% vs 6%) than the other breast carcinomas. Microcalcifications were less common (24% vs 41%) and retraction of the skin (25% vs 21%) and nipple (26% vs 17%) was more common in pure ILC than in the other breast carcinomas. When complementary magnification views were obtained, only 50% were helpful in diagnosis of ILC while 75% were helpful in diagnosis of other breast carcinomas. Malignancy was less frequently diagnosed in ILC (57%) than in the other breast carcinomas (64%). The results were intermediate in the mixed ILC group.

Adult↗

Cortical streams of visual information processing in primates.

1. The topographic organization of the cortical visual areas in the Cebus monkey and their anatomical connections support the subdivision of the visual pathways into ventral and dorsal streams of visual information processing. 2. We propose that the dorsal stream, as defined by Ungerleider and Mishkin (In: Ingle DJ, Goodale MA and Mansfield RJW (Editors), Analysis of Visual Behavior. MIT Press, Boston, 1982), be subdivided into dorsolateral and dorsomedial streams, which are concerned with different aspects of the processing of motion and spatial perception. 3. The data support the hypothesis of concurrent, modular processing of visual attributes in cortical visual areas in the different streams, and highlight some features of the visual field representation in each area which may reflect functional specialization of these streams. 4. The visual topography is locally disrupted in some cortical areas by the existence of functionally different modules. However, a global visuotopic organization is preserved in most areas. 5. The visuotopic organization may provide the address of space coordinates to integrate information concerning the same retinotopic locus across different visual areas.

Animals↗