Biomedical subjects

T Pietsch

Publications and source records attributed to T Pietsch.

At least 73 records · Page 4Linked to original sources

PubMed1998

Medullomyoblastoma: a histological, immunohistochemical, ultrastructural and molecular genetic study.

Medullomyoblastoma is a rare variant of medulloblastoma containing myoblastic elements. A 9-year-old boy developed a cerebellar syndrome and signs of increased intracranial pressure, the cause of which was a tumor of the cerebellar vermis measuring 7 x 4.5 x 4.5 cm. Morphologically the tumor largely consisted of a medulloblastoma component but displayed glial, myoblastic and ganglionic differentiation on light microscopic, immunohistochemical and ultrastructural examination. The non-enhancing rim of the tumor on magnetic resonance imaging showed extensive ganglionic differentiation. The tumor did not express bcl-2, c-myc, or c-erb-B2 oncoproteins and was negative for the p53 gene product. On molecular genetic studies, the tumor did not show allelic loss on chromosome loci, frequently altered in medulloblastomas, such as 17p, 1q and 9q.

Cerebellar Neoplasms↗

PubMed1998

Activation of the CD95 (APO-1/Fas) pathway in drug- and gamma-irradiation-induced apoptosis of brain tumor cells.

Chemotherapeutic agents and gamma-irradiation used in the treatment of brain tumors, the most common solid tumors of childhood, have been shown to act primarily by inducing apoptosis. Here, we report that activation of the CD95 pathway was involved in drug- and gamma-irradiation-induced apoptosis of medulloblastoma and glioblastoma cells. Upon treatment CD95 ligand (CD95-L) was induced that stimulated the CD95 pathway by crosslinking CD95 via an autocrine/paracrine loop. Blocking CD95-L/receptor interaction using F(ab')2 anti-CD95 antibody fragments strongly reduced apoptosis. Apoptosis depended on activation of caspases (interleukin 1beta-converting enzyme/Ced-3 like proteases) as it was almost completely abrograted by the broad range caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone. Apoptosis was mediated by cleavage of the receptor proximal caspase FLICE/MACH (caspase-8) and the downstream caspase CPP32 (caspase-3, Apopain) resulting in cleavage of the prototype caspase substrate PARP. Moreover, CD95 was upregulated in wild-type p53 cells thereby increasing responsiveness towards CD95 triggering. Since activation of the CD95 system upon treatment was also found in primary medulloblastoma cells ex vivo, these findings may have implications to define chemosensitivity and to develop novel therapeutic strategies in the management of malignant brain tumors.

Amino Acid Chloromethyl Ketones↗

PubMed1998

The occurrence of liver growth factor in hepatoblastoma.

Rapid growth of recurrent disseminated tumor and/or metastases can occur in children after incompletely resected, non-pretreated malignant hepatoblastoma (HB). This accelerated tumor growth is observed during the first four postoperative weeks, which is the period of maximal liver regeneration. One key regulator of regeneration, the hepatocyte growth factor (HGF), may be responsible for the induction of tumor growth. We, therefore, investigated levels and sources of HGF in HB patients. With ELISA we measured elevated serum levels (> 1,000 pg/ml) of HGF in 10 of 23 HB patients in comparison with three healthy children (< 610 pg/ml). HGF values of non-pretreated children with HB ranged from 169-10,183 pg/ml (mean 889 pg/ml) while those of patients after primary chemotherapy reached 608-15,000 pg/ml (mean 4,556 pg/ml). An up to fourfold increase of HGF was detected in 10 of 12 children 24-72 hours after liver resection. With immunoenzymatic staining on cryostat sections and cytospin preparations of the tumors we could localize HGF to the fibroblasts of the mesenchymal tumor components. In contrast, its receptor (c-met) was found to be expressed on the epithelial HB cells. Our results indicate that HGF secretion is enhanced after liver resection in children with HB and thus could have a biological function for growth of HGF receptor-expressing tumor cells. The results of immunostaining further suggest that HB is able to produce HGF as its own growth factor in a local paracrine fashion.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

A rapid and sensitive protocol for competitive reverse transcriptase (cRT) PCR analysis of cellular genes.

The specific analysis of gene transcripts is of increasing importance for studies in molecular pathology. Competitive RT-PCR with mutagenized exogenous competitor templates has evolved as an attractive approach to quantify individual mRNA levels. The generation of exogenous competitor RNAs usually requires mutagenesis and cloning of the mutant fragment into plasmids followed by in vitro transcription. In contrast to primer directed mutagenesis and in vitro transcription, preparation of the mutant fragments is a time consuming procedure. Here we report on a modified semi-quantitative RT-PCR protocol to circumvent the laborious cloning of mutant exogenous competitors. Templates for the in vitro transcription are generated in a single PCR reaction with simultaneous addition of a promoter sequence 5'of the forward primer and deletion of 10-20 nucleotides at the opposite end just ahead of the reverse primer binding site. The product of this PCR step serves as template for in vitro transcription to yield exogenous competitor RNA of equal quality and amount as conventional cloning strategies. Total RNA amounts are corrected for by analyzing the expression of different housekeeping genes in the same manner. One of the primers used in the following competitive RT-PCR reaction is labeled with a fluorescent dye for the analysis of target and exogenous competitor product on an semiautomated sequencer. In the present study, this protocol was employed to analyze the expression of the PTCH, Fas-receptor, NF-1, beta2-microglobulin and GAPD genes in human brain tumors. It will, however, be widely applicable to studies on cellular transcripts in biological specimens.

Binding, Competitive↗

PubMed1998

Developmental-dependent DNA methylation of the IGF2 and H19 promoters is correlated to the promoter activities in human liver development.

We have previously shown that the four promoters of the IGF2 gene are under a tight but dynamic control during human liver development, whereby P3 and P1 are reciprocally active before and after birth respectively while the P2 and P4 promoters are constitutively active at a relatively lower level. In this study, we investigated the methylation status of the promoters P1 and P3 of IGF2 and the promoter region of the H19 gene in developing human livers ranging from fetal to late adult. A region of about 300 bp immediately upstream of the IGF2 exon 5 was found to be subjected to a developmental-specific methylation and this may correlate to the P3 promoter activity. The P1 domain of IGF2 was also found to be methylated in a developmentally-specific pattern. The promoter region of the H19 gene displayed different methylation patterns in different development stages showing decreased general methylation with increase of age. Therefore, regional- and developmental-specific DNA methylation is displayed in the promoter regions of the IGF2 and H19 genes. This may be an important factor involved in gene regulation in the developing human liver.

Adult↗

PubMed1997

Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched.

Inactivating mutations in the PTCH gene, a human homologue of the Drosophila segment polarity gene patched, have been identified recently in patients with nevoid basal cell carcinoma syndrome. These patients are predisposed to various neoplasias including basal cell carcinomas and medulloblastomas (MBs). To determine the involvement of PTCH in sporadic MBs, which represent the most frequent malignant brain tumors in children, we screened for PTCH alterations in an unselected panel of 64 biopsy samples from 62 patients and four continuous MB cell lines, all derived from patients with sporadic MBs. Using single-strand conformational polymorphism analysis, we screened exons 2-22 and detected nonconservative PTCH mutations in 3 of 11 samples from sporadic cases of the desmoplastic variant of MB but none in 57 MBs with classical (nondesmoplastic) histology. In two of the tumors with mutations and in two additional desmoplastic cases, loss of heterozygosity was found at 9q22. These findings suggest that PTCH represents a tumor suppressor gene involved in the development of the desmoplastic variant of MB.

Adolescent↗

PubMed1997

Animal model of human medulloblastoma: clinical, magnetic resonance imaging, and histopathological findings after intra-cisternal injection of MHH-MED-1 cells into nude rats.

To establish an animal model of human medulloblastoma, we have injected human MHH-MED-1 cells into the cisterna magna of nude rats. Tumors grew in 3 out of 4 animals injected with 10(6) medulloblastoma cells. Affected animals showed little or no weight gain and eventually lost weight but did not develop obvious neurological symptoms until the end of observation on day 31 after inoculation. At this time, magnetic resonance imaging (MRI) in tumor-bearing rats revealed contrast enhancement in the region of the fourth ventricle and the cisterna magna. Neuropathological examination demonstrated corresponding leptomeningeal growth in the cisterna magna invading the medulla oblongata, and tumor growth within the fourth ventricle invading the pons. The tumors basically showed the same immunostaining pattern as MHH-MED-1 cells in vitro expressing neuron-specific enolase (NSE) and vimentin, but no neurofilaments (NFs), synapthophysin, or glial fibrillary acidic protein (GFAP). No tumor grew in the fourth animal, which had a normal weight gain and no alteration on MRI. In conclusion (1) the intrathecally injected human medulloblastoma cells spread similar to medulloblastomas in patients, (2) tumor growth is readily detected by MRI, (3) the new animal model is a suitable tool for further experimental research including intrathecal therapeutic studies.

Animals↗

PubMed1997

Tuberous sclerosis-like lesions in epileptogenic human neocortex lack allelic loss at the TSC1 and TSC2 regions.

Glioneuronal malformations with a striking histological resemblance to cortical tubers of tuberous sclerosis, but no extracerebral stigmata of this phacomatosis, are frequently encountered in patients with chronic pharmacoresistant epilepsies. It is controversial as to whether these lesion represent a forme fruste of tuberous sclerosis or a distinct entity. The recently reported loss of heterozygosity (LOH) at the regions of the TSC1 or TSC2 locus in hamartomas obtained from different organs of patients with established tuberous sclerosis, including cortical tubers, stimulated us to examine epilepsy-associated tuberous sclerosis-like glioneuronal malformations with respect to LOH at the TSC1 and TSC2 loci of chromosomes 9q34 and 16p 13.3, respectively. The analysis was carried out on DNA derived from paraffin-embedded brain tissues of 11 patients. For 5 patients, peripheral blood leukocytes were also available for DNA extraction. We performed microsatellite analysis with five markers on chromosome 9 and four markers on chromosome 16. In addition, polymerase chain reaction-restriction fragment length polymorphism (RFLP) analysis was performed using a polymorphic EcoRV restriction site in exon 40 of the TSC2 gene. No LOH was identified in any of the cases. These findings do not support a relationship between the epilepsy-associated glioneuronal lesions and tuberous sclerosis. However, tuberous sclerosis is genetically heterogeneous and microsatellite and RFLP analysis cannot exclude small deletions or point mutations. Thus, given the histopathological similarity of glioneuronal malformations in epilepsy patients to cortical tubers, further molecular genetic studies will be needed as our understanding of the molecular basis of tuberous sclerosis increases to completely clarify the relationship of these lesions to tuberous sclerosis.

Adolescent↗

PubMed1997

Expression and distribution of vascular endothelial growth factor protein in human brain tumors.

Marked neovascularization is a hallmark of many neoplasms in the nervous system. Recent reports indicate that the endothelial mitogen vascular endothelial growth factor (VEGF) may play a critical role in the regulation of vascular endothelial proliferation in malignant gliomas. Using novel monoclonal antibodies to the VEGF polypeptide we have determined the expression and cellular distribution of VEGF protein in a representative series of 171 human central nervous system (CNS) tumors by immunohistochemistry and immunoblotting. In agreement with previous in situ hybridization data, 19 out of 20 glioblastomas (95%) showed immunoreactivity for VEGF, whereas both the percentage of immunoreactive tumors and the extent of immunoreactivity for VEGF were significantly lower in astrocytomas. Of the pilocytic astrocytomas (WHO grade I) 44% were immunoreactive for VEGF, but we observed several cases with pronounced vascular proliferates in the absence of VEGF. In ependymomas, meningiomas, hemangioblastomas, and primitive neuroectodermal tumors, there was no correlation between VEGF expression, vascular endothelial proliferation and the grade of malignancy. Oligodendrogliomas and the oligodendroglial component of mixed gliomas lacked immunoreactive VEGF, indicating that endothelial growth factors other than VEGF may regulate tumor angiogenesis in these neoplasms. Western blot analysis showed a predominant VEGF protein species of 23 kDa and confirmed the immunohistochemical data in all cases. Our findings demonstrate that VEGF is expressed in a wide spectrum of brain tumors in which it may induce neovascularization. However, other angiogenic factors also appear to contribute to the vascularization of CNS neoplasms.

Astrocytoma↗

PubMed1997

Neural antigens in oligodendrogliomas and dysembryoplastic neuroepithelial tumors.

Oligodendrogliomas and dysembryoplastic neuroepithelial tumors (DNT) are frequently associated with epilepsies and share the presence of oligodendroglia-like cells with small round nuclei and optically empty perinuclear halos. The two entities may be difficult to discriminate in small surgical specimens and the origin and differentiation of the oligodendroglia-like cells has been controversial. To better characterize and distinguish the two entities we examined 25 oligodendrogliomas and 16 DNT immunohistochemically for the presence of the proliferation-associated Ki-67 antigen and the following neural antigens: the alpha 1 subunit of the GABAA receptor (GABAR), N-methyl-D-aspartate receptor subunit 1 (NR1), glutamate decarboxylase, neuronal nuclei antigen (NeuN), the embryonal form of the neural cell adhesion molecule (E-NCAM), synaptophysin, neurofilament protein (NFP), and glial fibrillary acidic protein (GFAP). Labeling indices for the Ki-67 antigens were generally less than 1% in both entities. In oligodendrogliomas, more than 50% of the tumors contained NR1- or E-NCAM-positive oligodendroglia-like cells, whereas NeuN-positive tumor cells were never observed. In DNT, NeuN- and NR1-positive tumor cells were present in 44% of the cases each; E-NCAM positivity was less frequent (19%). In both entities, immunoreactivity of oligodendroglia-like cells for GABAR and glutamate decarboxylase was rare and positivity for synaptophysin and neurofilament protein was absent. Some GFAP-positive tumor cells were present in approximately 70% of the cases in both entities. Except for the striking difference in NeuN positivity, the immunohistochemical profiles of oligodendroglia-like cells in DNT and oligodendrogliomas largely overlap and the differential diagnosis continues to rest mainly on conventional histopathological features. The NR1 positivity and the recently reported generation of action potentials in oligodendroglioma cells are consistent with neuronal differentiation and may contribute to the high epileptogenic potential of oligodendrogliomas.

Adult↗

PubMed1997

Molecular neuropathology of astrocytic brain tumors.

Both surgical and molecular neuropathologists have recently achieved remarkable progress in the histogenetic classification and molecular characterization of human gliomas. Major histopathological achievements in the revised WHO classification include the introduction of immunohistochemical reagents for glial fibrillary acidic protein and for the proliferation-associated antigens, the definition of glioblastoma multiforme as an astrocytic neoplasm and the recognition of the pleomorphic xantho--astrocytomas as a novel clinico-pathological entity. In molecular neuropathology, alterations of oncogenes and tumor suppressor genes and their potential functions have been identified, microsatellite analyses have revealed novel loci for putative tumor suppressor genes and distinct molecular pathways for different tumor entities are beginning to emerge. Mutations in cell cycle regulatory genes are present in most glioblastomas and may account for their striking growth potential. Autocrine and paracrine growth factors and their respective protein tyrosine kinase receptors appear to contribute both to glial and endothelial cell proliferation. In our contribution, we would like to focus on astrocytic gliomas. Findings with potential diagnostic relevance include changes associated with malignant progression of low grade astrocytomas, patterns of genetic alterations which allow to further differentiate histopathological entities such as the glioblastoma multiforme into genetically distinct subsets and mechanisms of tumor angiogenesis in malignant gliomas. One of the major tasks ahead is to establish correlations and relationships between histopathological, molecular and clinical data. This will require a long-term collaboration between molecular neuropathologists, neurosurgeons and clinical neuro-oncologists.

Animals↗

PubMed1997

Metabolic studies of human primitive neuroectodermal tumour cells by proton nuclear magnetic resonance spectroscopy.

Well-characterized cell lines established from primitive neuroectodermal tumours (PNETs) were examined by proton nuclear magnetic resonance (1H-NMR) spectroscopy and chromatographic analysis of perchloric acid extracts, following amplification in cell culture. A characteristic 1H-NMR spectroscopic metabolite pattern was found for medulloblastoma cell lines, which clearly discriminates these cells from PNETs of other locations in the central nervous system (CNS), on the basis of their N-acetyl aspartate (NAA) and aspartate expression. Medulloblastoma cell lines were heterogeneous in respect of their metabolite expression, possibly owing to the heterogeneity in their differentiation along lineages of the CNS. All PNET spectra displayed similar features, including decreased NAA and creatine peaks and increased signals from choline compounds (Cho) compared with normal cerebellum. The expression of NAA by the medulloblastoma lines was in the opposite order to the extent of neuronal differentiation, which may indicate their origin from a progenitor cell with the phenotype of an oligodendrocyte-type-2 astrocyte cell.

Aspartic Acid↗

PubMed1997

Hepatic stem-like cells in hepatoblastoma: expression of cytokeratin 7, albumin and oval cell associated antigens detected by OV-1 and OV-6.

AIMS: In a recent study we described a population of small epithelial cells (SEC) in human hepatoblastoma that exhibit ultrastructural features of the oval cell of rodents. Both SEC and oval cells are immunoreactive for cytokeratin 7, a marker of biliary differentiation, and it was postulated that SEC, like oval cells, are closely related to hepatic stem cells. This study was undertaken to investigate whether SEC also exhibit immunolabelling for albumin, a marker of hepatocytic differentiation, and to determine whether other antigens typical of oval cells are detectable in hepatoblastoma. METHODS AND RESULTS: Hepatoblastomas of various subtypes were investigated by electron microscopy, and by immunohistochemistry with the monoclonal antibodies OV-1 and OV-6, which recognize antigens associated with oval cells. Double-labelling for cytokeratin 7 and albumin was carried out by immuno-electron microscopy. OV-1 stained scattered cells in seven of 12 tumours investigated and OV-6 in nine. On immunoelectron-microscopic investigation, SEC exhibited labelling for both cytokeratin 7 and albumin. CONCLUSIONS: The results demonstrate that antigens associated with oval cells are found in certain cells in hepatoblastoma. SEC, like oval cells, co-express markers for hepatocytic and biliary differentiation. The findings further support the hypothesis that SEC are closely related to the putative bipotent hepatic stem cell, which, by definition, gives rise to both hepatocytes and biliary epithelial cells.

Albumins↗

PubMed1997

Characterization of neural cell lines derived from SV40 large T-induced primitive neuroectodermal tumors.

We recently reported intriguing properties of neural tumors generated by retrovirus-mediated transfer of the SV40 large T antigen into fetal rat brain transplants. Histopathologically, these neoplasms displayed characteristic features of primitive neuroectodermal tumors (PNET) and exhibited a striking potential for migration into the host brain. In the present study, four cell lines were derived from these PNETs and characterized. Two lines with an immature phenotype expressed the embryonal form of the neural cell adhesion molecule and nestin. They showed spheroid formation and delicate cell processes. The remaining cell lines had a flat, epitheloid appearance and were immunoreactive for synaptophysin, neurofilament proteins and glial fibrillary acidic protein. These cells constitute valuable tools to study the cellular origin(s) and molecular basis of PNETs, differentiation of neural progenitors and tumor cell migration in the brain.

Animals↗

PubMed1997

Specificity and functional effects of antibodies to human stem cell factor.

Three monoclonal antibodies (Mabs), 7H6, 4B10 and Genzyme Mab, and a commercially-available polyclonal antiserum (Genzyme) to human Stem Cell Factor (SCF) were compared for their ability to detect native and recombinant SCF in a variety of assays, and for blocking of SCF function. All antibodies were found to bind to the membrane bound isoform as well as soluble SCF and to bind to both glycosylated (yeast MGF) and unglycosylated (E. coli SCF) recombinant factor. Mabs 7H6 and 4B10, as well as the polyclonal antiserum could immunoprecipitate membrane-associated SCF and all the antibodies could detect recombinant soluble SCF on western blots, although the binding of all except 7H6 was partially sensitive to reduction. Titration of the antibodies on CHO cells expressing membrane-associated human SCF showed similar dose-dependence for all Mabs with 70% of maximum binding seen at 3, 5 and 8 micrograms/ml for 7H6, 4B10 and Genzyme Mab respectively, however the maximum binding seen with 7H6 was approximately 2-fold greater than with 4B10 and 7-fold greater than Genzyme Mab. Competitive binding experiments of the Mabs on cells expressing membrane SCF gave non-reciprocal blocking in all cases with 7H6 completely blocking 4B10 and Genzyme Mab binding. All antibodies except the Genzyme Mab effectively blocked SCF binding to c-Kit-expressing cells, and were strongly inhibitory in an assay of in vitro haemopoiesis which is believed to depend on adhesive interactions, as well as the "classical' cytokine-receptor interaction, mediated by SCF binding to c-Kit.

Animals↗

PubMed1996

Loss of heterozygosity on chromosome 1 in human hepatoblastoma.

In previous studies we have found loss of heterozygosity (LOH) on chromosome arm 11p in 33% of hepatoblastomas (HBs). In addition, cytogenetic studies have revealed aberrations of chromosome arm 1p in single cases. Therefore, we have used the PCR to amplify 10 microsatellites on the short arm and 7 microsatellites on the long arm of chromosome I to assess allelic loss in 32 cases of HB. LOH on chromosome I was found in II cases. Seven HBs showed LOH on chromosome Ip, 7 cases had LOH on Iq, and 3 tumors had LOH on both Ip and Iq. Six HBs with LOH on Ip had LOH at DIS243 (Ip36.3), and one tumor had a loss at DIS80 maintaining heterozygosity at DIS243. A common region of overlap was present at the telomeric chromosomal portion of Ip between DIS80 and DIS243. Of the HBs with LOH on Iq, 4 showed a common region of overlap at Iq3I-q32.I, and the other 3 at DISI609 located more telomerically. The parental origin of the lost allele was of random distribution for chromosome arm Ip and of paternal origin for chromosome arm Iq. Our data suggest that tumor suppressor genes located at the telomeric region of chromosome arm Ip and different regions of chromosome arm Iq may be involved in the pathogenesis of HB.

Adolescent↗

PubMed1996

Loss of heterozygosity at locus F13B on chromosome 1q in human medulloblastoma.

Medulloblastoma is a primitive neuroectodermal tumor of the cerebellum with poorly understood pathogenesis. Previous studies have reported loss of heterozygosity (LOH) on chromosome arms 17p, 11p and 9q and cytogenetic abnormalities of chromosome 1 in medulloblastoma. We have used the polymerase chain reaction to amplify 10 microsatellites on the short arm and 8 microsatellites on the long arm of chromosome 1 to assess allelic loss in 22 medulloblastomas. Loss of heterozygosity (LOH) on chromosome 1 was found in 9 cases. Eight medulloblastomas (36%) showed an interstitial LOH on chromosome 1q. The common region of overlap was mapped between D1S 1604 and D1S237 and included the locus F13B in the chromosomal region 1q31-q32.1. An additional tumor had LOH in a proximal region of 1p, but did not exhibit LOH on 1q. None of the medulloblastomas exhibited LOH of the telomeric portion of chromosome 1p, which has been associated with several other human malignancies. Our data suggest the presence of a putative tumor suppressor gene located near the locus F13B on chromosome arm 1q that appears to be involved in the pathogenesis of medulloblastoma.

Adolescent↗

PubMed1996

Fetal- and tumor-specific regulation of growth hormone receptor messenger RNA expression in human liver.

Eight different 5'-untranslated region variants of the human growth hormone receptor (hGHR) mRNA have been identified in adult liver (V1-V8). We have compared the expression of two of these variants (V1 and V3) in several human fetal and postnatal tissues (including liver) as well as in hepatoblastomas (HBs) and hepatocellular carcinomas (HCCs). Using reverse transcription-PCR assays, followed by Southern blotting to confirm the specificity of the amplified fragments, we found that V3 was expressed in all fetal and postnatal liver (n = 13 fetal and 5 postnatal), kidney (n = 4 fetal and 4 postnatal), lung (n = 4 fetal and 2 postnatal), intestine (n = 8 fetal and 4 postnatal), skeletal muscle (n = 1 fetal and 1 postnatal), and adrenal (n = 1 fetal and 1 postnatal) samples. In contrast, V1 was expressed only in postnatal liver. We then screened for V1 and V3 in HBs (n = 17, ages 6-36 months, including 5 with paired normal liver), and HCCs (n = 4, ages 50-75 years, with paired normal liver). V1 was undetectable in 15 of 17 HBs, including all HBs paired with (V1-expressing) normal liver; the absence of V1 did not correlate with patient age, sex, HB subtype, +/- chemotherapy, exon 3-retaining and -deficient hGHR mRNA isoform pattern, or loss of heterozygosity at 11p, 1p, and 1q. The four HCCs showed marked (>20-fold; n = 2) or complete (n = 2) suppression of V1 as compared to paired normal liver. V3 was expressed in all HBs, HCCs, and paired normal livers. Interestingly, V3, but not V1, was detected in two Wilms' tumor and paired normal kidney specimens. Our findings suggest that, in the human, there is tissue-, fetal- and tumor-specific regulation of V1 hGHR mRNA.

Adolescent↗