PubMed Health⌕ Search

Biomedical subjects

F Hedborg

Publications and source records attributed to F Hedborg.

27 records · Page 2Linked to original sources
PubMed1994

Trk mRNA and low affinity nerve growth factor receptor mRNA expression and triploid DNA content in favorable neuroblastoma tumors.

Nerve growth factor (NGF) is suggested to play a role in spontaneous differentiation or regression of neuroblastoma. Expression of mRNAs for trk protooncogene and NGF low affinity receptor gene (LNGFR) were analyzed in 45 neuroblastomas with Northern Blot. Trk and LNGFR expression correlated with young age, localized tumors or IV-S disease, absence of N-myc amplification, triploid DNA content, spontaneous tumor regression and favorable prognosis. Regardless of other factors, trk and LNGFR mRNAs distinguished three prognostic subsets: one favorable (trk+, LNGFR+, n = 19, 100% survival probability), one intermediate (trk+, LNGFR-, n = 11, 62%) and one poor (trk-, n = 15, 0%). An algorithm based on the combined analysis of trk and LNGFR mRNAs and DNA ploidy divided the material in two groups with 96 and 0% survival probability respectively (p < 0.001), and predicted outcome accurately in 43 of 45 children. It is hypothesized that loss of functional NGF-receptors constitutes an early critical step in the evolution of unfavorable neuroblastomas prone to progression in spite of current therapy.

DNA, Neoplasm↗
PubMed1993

Tight linkage between the Beckwith-Wiedemann syndrome and a microsatellite marker for the TH locus.

The Beckwith-Wiedemann syndrome (BWS) is characterized by somatic overgrowth, developmental anomalies, and proneness to embryonic tumor development. The majority of cases are sporadic, but several families with an autosomal dominant mode of inheritance with variable expression and reduced penetrance have been described. In three such families, BWS has been linked to DNA markers for the insulin gene (INS) and H-ras on chromosome band 11p15. Two additional families with inherited BWS are described here. Linkage analysis has been performed with a highly informative marker for the tyrosine hydroxylase (TH) locus within the INS-IGF2 (insulin-like growth factor II)-TH gene cluster and confirms the previous observed linkage to this region (lod score 2.16 at theta = 0). Linkage analysis to TH provides a basis for informed genetic counselling and carrier detection in the hereditary form of the syndrome. Based on the hypothesis that IGF2 may be a candidate gene for BWS, we screened for mutations in the coding exons 7 and 9, but found no abnormalities in 5 unrelated BWS cases.

Beckwith-Wiedemann Syndrome↗
PubMed1993

IGF2 is parentally imprinted during human embryogenesis and in the Beckwith-Wiedemann syndrome.

The phenomenon of parental imprinting involves the preferential expression of one parental allele of a subset of chromosomal genes and has so far only been documented in the mouse. We show here, by exploiting sequence polymorphisms in exon nine of the human insulin-like growth factor 2 (IGF2) gene, that only the paternally-inherited allele is active in embryonic and extra-embryonic cells from first trimester pregnancies. In addition, only the paternal allele is expressed in tissues from a patient who suffered from Beckwith-Wiedemann syndrome. Thus the parental imprinting of IGF2 appears to be evolutionarily conserved from mouse to man and has implications for the generation of the Beckwith-Wiedemann syndrome.

Alleles↗
PubMed1993

Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment.

PURPOSE AND METHODS: Based on preliminary experience, there was a need for modifications and clarifications in the International Neuroblastoma Staging System (INSS) and International Neuroblastoma Response Criteria (INRC). In 1988, a proposal was made to establish an internationally accepted staging system for neuroblastoma, as well as consistent criteria for confirming the diagnosis and determining response to therapy (Brodeur GM, et al: J Clin Oncol 6:1874-1881, 1988). A meeting was held to review experience with the INSS and INRC and to revise or clarify the language and intent of the originally proposed criteria. Substantial changes included a redefinition of the midline, restrictions on age and bone marrow involvement for stage 4S, and the recommendation that meta-iodobenzylguanidine (MIBG) scanning be implemented for evaluating the extent of disease. Other modifications and clarifications of the INSS and INRC are presented. In addition, the criteria for the diagnosis of neuroblastoma were modified. Finally, proposals were made for the development of risk groups that incorporate both clinical and biologic features in the prediction of prognosis. The biologic features that were deemed important to evaluate prospectively included serum ferritin, neuron-specific enolase (NSE), and lactic dehydrogenase (LDH); tumor histology; tumor-cell DNA content; assessment of N-myc copy number; assessment of 1p deletion by cytogenetic or molecular methods; and TRK-A expression. RESULTS AND CONCLUSION: Modifications of the INSS and INRC made at this conference are presented. In addition, proposals are made for future modifications in these criteria and for the development of International Neuroblastoma Risk Groups.

Humans↗
PubMed1992

Chromosome aberrations in an alpha-fetoprotein-producing hepatoblastoma.

The cytogenetic findings of an alpha-fetoprotein (AFP)-producing hepatoblastoma in a 14-month-old girl are reported. Ten of 36 tumor cells were chromosomally abnormal, yielding the composite karyotype 47,XX,2q +, t(3;5)(p25;q31),dup(4)(q12q26), +20. Three of the chromosomal abnormalities (2q+, break at 4q12, +20) have been reported previously and might be of pathogenetic significance.

Aneuploidy↗
PubMed1992

N-myc gene amplification in neuroblastoma: a clinical approach using ultrasound guided cutting needle biopsies collected at diagnosis.

N-myc gene amplification was studied in a consecutive series of neuroblastomas and ganglioneuromas, representing all of such tumours diagnosed in Sweden over a 4-year period. Both frozen and formalin fixed specimens were used for Southern blot analysis. Thirty-seven of 46 neuroblastomas and 7 of 9 ganglioneuromas were analyzed. Seven neuroblastomas and none of the ganglioneuromas showed N-myc gene amplification. All children with amplified tumours, including three infants, had advanced disease at diagnosis and aggressive course of disease. However, follow-up time was short for the two cases still alive. The use of an ultrasound guided cutting needle biopsy technique for obtaining the required tissue at diagnosis was evaluated in some cases. This technique appeared to be safe and clinically useful since early prognostic information was obtained. Using an imprint from the needle biopsy, the representativity could be confirmed. Ultrasound guided cutting needle biopsies can thus be used routinely to obtain N-myc gene amplification data prior to initiation of therapy in neuroblastoma.

Biopsy, Needle↗
PubMed1990

Expression of the neuronal form of pp60c-src in neuroblastoma in relation to clinical stage and prognosis.

The expression of the protooncogene c-src has been studied in specimens of childhood tumors with special reference to neuroblastoma and other tumors of neuronal origin. For comparison c-src gene expression was studied in seven neuroblastoma and neuroepithelioma cell lines. The structurally distinct neuronal product of the gene, pp60c-srN, expressed during normal development in neuroblasts and neurons, was identified by immunoblotting technique together with the fibroblast form, pp60c-src. While pp60c-src was found in most tumors studied, the neuronal form was restricted to neuroblastomas (23 of 27) and retinoblastomas (3 of 3) and could not be detected in the other childhood tumors. A dominance of the neuronal form, pp60c-srcN, was exclusively found in the infant cases of neuroblastoma (9 of 12), estimated to have good prognosis. These results indicate that pp60c-srcN might be a diagnostic marker in primitive childhood tumors. When expressed in higher amounts than pp60c-src, pp60c-srcN may be a positive prognostic marker in neuroblastoma, especially useful in the evaluation of infants. In addition, lack of pp60c-srcN seems to be incompatible with low stage neuroblastoma.

Aging↗