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A Hochberg

Publications and source records attributed to A Hochberg.

At least 37 records · Page 2Linked to original sources
PubMed1998

Endothelial nitric oxide synthase immunoreactivity in early gestation and in trophoblastic disease.

AIMS: To study the localisation of the endothelial nitric oxide synthase (eNOS) in the normal placenta, with special emphasis on the implantation site in the first trimester of pregnancy, and in the different subtypes of trophoblastic cells in gestational trophoblastic disease. METHODS: The immunoperoxidase technique with an antibody directed against eNOS was applied to paraffin sections from first and second trimester placentas, placenta accreta, partial and complete hydatidiform moles, and choriocarcinoma. Immunoperoxidase staining for human placental lactogen (hPL) was performed on parallel sections. RESULTS: Prominent immunoreactivity for eNOS was found to be present in the intermediate trophoblastic cells of the cell columns of the anchoring villi and in trophoblastic cells at the implantation site. Staining was also present in the syncytiotrophoblast, most conspicuous at the apical cell border. In trophoblastic disease, proliferating large mononuclear cells, which were strongly positive for hPL, were found to be immunoreactive for eNOS. CONCLUSIONS: eNOS immunoreactivity is strongly positive in the extravillous trophoblastic cells and to a lesser extent in the syncytiotrophoblast. In the former it may play a role in implantation and vascular invasion. Cells with differentiation to intermediate trophoblast in complete hydatidiform mole and choriocarcinoma also show high levels of eNOS, which may be associated with the haematogenous mode of spread of trophoblastic disease.

Choriocarcinoma↗
PubMed1998

Imprinted H19 oncofetal RNA is a candidate tumour marker for hepatocellular carcinoma.

AIMS/BACKGROUND: To study the expression of the H19 gene in hepatocellular carcinoma. H19 is an imprinted, maternally expressed gene, which is tightly linked, both physically and functionally, to the paternally expressed insulin-like growth factor 2 (IGF II). IGF II is known to be involved in liver carcinogenesis. H19 was first discovered in the fetal mouse liver to be under the same regulatory genes as alpha fetoprotein (alpha FP), a widely used tumour marker for hepatocellular carcinoma. METHODS: Using both radioactive and non-radioactive in situ hybridisation, the expression of the H19 gene was compared with the presence of alpha FP, as demonstrated by immunohistochemistry, in 18 cases of hepatocellular carcinoma. RESULTS: H19 expression was present in 13 of 18 cases, whereas staining for alpha FP was positive in only nine of 18 cases. Concordance was found in 12 of 18 tumours (66.7%). In general, the staining pattern for H19 was more diffuse than the immunohistochemical staining for alpha FP. CONCLUSIONS: The addition of a non-radioactive in situ hybridisation assay for H19 RNA to the panel of tumour markers used for the histopathological and cytological diagnosis of hepatocellular carcinoma might be useful.

Adult↗
PubMed1997

The expression of the imprinted genes H19 and IGF-2 in choriocarcinoma cell lines. Is H19 a tumor suppressor gene?

H19 is a paternally imprinted gene with unknown function. It is located in close proximity to the maternally imprinted IGF-2 gene on chromosome 11p15.5. In this study no consistent relationship between the expression of these two genes in clones derived from JEG-3 and JAr cell lines could be detected. Nor could a consistent relationship be detected between the expression levels of these two genes and between certain characteristic tumorigenic properties of these clones. We included in this study clones, expressing low H19 levels, which after transfection with an H19 expression construct highly expressed the H19 gene. In tumors, formed by the injection of cells of JAr or JEG-3 clones into nude mice, the H19 expression was high and irrelevant to the expression level in the cells before the injection. The same phenomenon was found for IGF-2 expression during tumorigenesis caused by cells of different JEG-3 clones and in some but not all JAr derived clones. Both H19 and IGF-2 are biallelicly expressed in all the JAr and JEG-3 clones. In summary, our observations point to the conclusion that H19 is not a tumor suppressor gene. However, its high expression in all the tumors formed after injection of cells of the JAr and JEG-3 clones, leaves its role, if any, in choriocarcinogenesis an open question.

Animals↗
PubMed1997

Time reversal in biological systems.

Fundamental physical laws provide us appropriate descriptions of the basic behavior of nature. Science possesses a hierarchical structure with various levels of complexity and organization. This extends from the physics of elementary particles and atomic constituents, to the chemistry of molecules, to the biology of the cell and multicellular levels, up to an individual and beyond. Molecular biology thus has its roots based upon fundamental physical descriptors of macromolecules and chemical reactions. The purpose of this paper is to relate an operation in physics, time reversal symmetry, to the realm of biology. This is done with regard to the process of carcinogenesis. Tumor development and progression can be considered a microcosm of evolution, on the level of an individual organism, as well as from the aspect of evolutionary lineage. The driving forces of selection inherent in malignancy can be considered to result in the emergence of a new biological species, which is characterized by reproductive immortality and a remarkable equivalence with our unicellular ancestors. Thus, by its very nature, carcinogenesis as a closed system conceptually represents a reversal of motion with respect to order, stability and evolutionary standards of time.

Animals↗
PubMed1997

Genomic imprinting and the endometrial cycle. The expression of the imprinted gene H19 in the human female reproductive organs.

H19 is an imprinted maternally expressed gene, which is not translated to protein and functions as an RNA molecule. It is closely related to the oppositely imprinted paternally expressed insulin-like growth factor 2 (IGF-2). While the biological function of H19 is not understood IGF-2 is a growth factor that plays a role in human follicular and endometrial differentiation. We examined the expression of H19 in the endometrium and ovary during the menstrual cycle by in situ hybridization applied to paraffin sections of human endometrium and ovaries at different stages of differentiation. In the endometrium, H19 expression was confined to the stroma and fluctuated with endometrial dating to reach its peak in the late secretory stage. IGF-2 was also prominently expressed in late secretory endometrium, but its expression was evident both in the stroma and glandular epithelium. Expression of H19 was not found in primordial, primary, and preantral follicles of the ovary, but prominent expression was evident in the theca of antral and cystic atretic follicles, and focal expression was noted in the granulosa of corpora lutea. An association between H19 expression during the menstrual cycle and the differentiation state of the human female reproductive tract, which is under hormonal control, is suggested.

Cell Differentiation↗
PubMed1997

The product of the imprinted H19 gene is an oncofetal RNA.

AIMS/BACKGROUND: The H19 gene is an imprinted, maternally expressed gene in humans. It is tightly linked and coregulated with the imprinted, paternally expressed gene of insulin-like growth factor 2. The H19 gene product is not translated into protein and functions as an RNA molecule. Although its role has been investigated for more than a decade, its biological function is still not understood fully. H19 is abundantly expressed in many tissues from early stages of embryogenesis through fetal life, and is down regulated postnatally. It is also expressed in certain childhood and adult tumours. This study was designed to screen the expression of H19 in human cancer and its relation to the expression of H19 in the fetus. METHODS: Using in situ hybridisation with a [35S] labelled probe, H19 mRNA was detected in paraffin wax sections of fetal tissues from the first and second trimesters of pregnancy and of a large array of human adult and childhood tumours arising from these tissues. RESULTS: The H19 gene is expressed in tumours arising from tissues which express this gene in fetal life. Its expression in the fetus and in cancer is closely linked with tissue differentiation. CONCLUSIONS: Based on these and previous data, H19 is neither a tumour suppressor gene nor an oncogene. Its product is an oncofetal RNA. The potential use of this RNA as a tumour marker should be evaluated.

Biomarkers, Tumor↗
PubMed1996

Characterization of the imprinted IPW gene: allelic expression in normal and tumorigenic human tissues.

IPW (Imprinted gene in the Prader-Willi syndrome region) is a recently identified paternally expressed gene. Previous work has demonstrated IPW expression in the human fetus and adult, with monoallelic expression in adult lymphoblasts and fibroblasts, and in fetal tissues. To further examine the expression of IPW, a series of experiments were carried out using RT-PCR to measure IPW expression in placentae and various fetal and tumor tissues. Biallelic expression of IPW was found in testicular germ cell tumor and bladder cancer cells, suggesting loss of imprinting in the latter case. Both H19 and Insulin-like growth Factor 2 (IGF2), two additional imprinted genes, also showed biallelic expression in those same tumors that demonstrated IPW biallelic expression. Of note, the naturally occurring parthenogenetic-derived mature teratoma unexpectedly expressed large amounts of IPW. Lastly, the pluripotent embryonal cancer cell line Tera-2 expressed IPW at the same level before and after differentiation induced by retinoic acid, suggesting that this gene functions in a 'housekeeping' capacity throughout cell growth. This was in contradistinction to H19 and IGF2, both of which showed significant transcriptional upregulation after Tera-2 cell differentiation.

Adult↗
PubMed1996

Relaxation of imprinting in carcinogenesis.

The study of genes at the heat of tumorigenesis has helped unveil an elaborate biochemical circuitry that governs the proliferation and differentiation of cells. Genomic imprinting is rapidly being recognized as a fundamental process in tumor biology. Aberrant relaxation of imprinted genes have been detected in a wide variety of cancers, of both embryonal and nonembryonal origin. However, despite a vast array of experimental observation, both the purpose and pathogenic mechanism of relaxation of imprinting remain an enigma. Hypotheses are examined in this regard along with speculation for future research.

Chromosome Aberrations↗
PubMed1996

Hyaluronan, CD44 and its variant exons in human trophoblast invasion and placental angiogenesis.

Both hyaluronan and one of its receptors, CD44, can be demonstrated in the early human conceptus and in placental stroma. The variants of CD44 resulting from variable exon splicing are found in metastasizing human malignancies and are also involved in hyaluronan uptake and degradation. The resulting hyaluronan fragments are known to be highly angiogenic. We postulated that the self-limited process of trophoblast invasion of the uterine decidua results in part from the strategy of alternative splicing of CD44, similar to that used by invasive cancer cells in the course of metastatic spread and possibly angiogenesis. Monoclonal antibodies specific for CD44s and for an exon expressed during metastatic tumour progression, CD44v7, were used to examine this hypothesis. In this study we found human trophoblasts, for the first time, to express CD44. Intermediate trophoblasts of first and second trimester exhibited the standard form of CD44 while extravillous trophoblasts, which are responsible for the invading characteristics of the placenta, were positive for the alternatively spliced form, the CD44v7-8. Moreover, in the case of placenta accreta there was a prominent membrane staining of the trophoblasts that were embedded in the fibrin layer over the myometrium. The highly metastatic choriocarcinoma cells also expressed CD44v7-8. We propose, therefore, that the invading trophoblasts utilize the alternatively splicing machinery. These cells retain their invasive capabilities through the permissive ECM by carrying the CD44v7-8 isoform, which binds weakly to hyaluronan and thus prevents it from being degraded by intracellular hyaluronidase.

Alternative Splicing↗
PubMed1996

Developmentally imprinted genes as markers for bladder tumor progression.

PURPOSE: Developmentally imprinted genes, such as H19 and insulin-like growth factor-II (IGF-II), play an important role during human embryogenesis and also have been implicated in the pathogenesis of embryonal tumors of childhood. Since H19 is expressed in human fetal bladder, we evaluated 35 bladder carcinomas for H19 expression by in situ hybridization analysis and correlated expression with tumor grade. As a prelude to gene transfer studies to determine if H19 is a bladder tumor oncogene, we also evaluated bladder cell lines for expression of H19, IGF-II, IGF-I and the type I IGF receptor. MATERIALS AND METHODS: H19 expression was evaluated by in situ hybridization analysis in bladder tumor specimens. Northern analysis was used to evaluate the expression of H19, IGF-II, IGF-I and the type I IGF receptor in bladder cell lines. RESULTS: H19 was expressed preferentially in advanced stage tumors: 2 of 12 grade I tumors were H19 positive, whereas 9 of 11 grade II and 7 of 10 grade III tumors expressed H19 (p = 0.004). Additionally, 6 of 6 carcinoma in situ tumors were H19 positive, whereas normal bladder mucosa cells were H19 negative. We found that 3 of 11 cell lines (HT-1376, HT-1197 and 5637) express high levels of H19 mRNA, and each of these cell lines and J82 also express IGF-II. All cell lines examined expressed the type I IGF receptor, whereas there was no detectable IGF-I mRNA. CONCLUSIONS: These data demonstrate that H19 is an oncodevelopmental marker of bladder tumor progression and raise the possibility that H19 may have oncogenic properties in bladder cancer.

Biomarkers, Tumor↗
PubMed1995

The expression of the imprinted H19 and IGF-2 genes in human bladder carcinoma.

The imprinted H19 gene is highly expressed in human embryos, fetal tissues and is nearly completely shut off in adults. However, it is reexpressed in a number of tumors including bladder carcinoma, demonstrating that H19 RNA is an oncofetal RNA. Tumors induced by injection of bladder carcinoma cell lines express H19 in contrast to the cells before injection. These observations support the notion of a positive correlation between H19 expression and bladder carcinoma. Loss of imprinting of H19 and IGF-2 was observed in samples of human bladder carcinoma.

Animals↗
PubMed1995

The interaction between cytotrophoblasts and their derived tumor cells.

Previous experiments demonstrated that human cytotrophoblasts and cells of the choriocarcinoma cell line JAr interact in vitro. As a result of this interaction there is an increased synthesis of CG and hPL, probably as a result of the increased CG and hPL synthesis by the cytotrophoblasts. In the present investigation we studied this interaction in greater detail and found that both cytotrophoblasts and JAr cells undergo changes in their biological properties as a result of this interaction. JAr cells and cytotrophoblasts cocultured for 72 hr were fractionated according to their size by centrifugal elutriation. The number of cells in the fraction which contain the largest cells was very significantly increased as a result of the coculture. This increase was due to an increase in the number of cells of both cell types. This fraction was the most active one in the synthesis of CG and hPL. The synthesis of DNA by the JAr nuclei in this fraction of the cocultured cells was almost completely inhibited but in the parallel fraction of the JAr cells cultivated alone the level of DNA synthesis was equal to that of all other JAr cell fractions. Heterokaryons are formed in the coculture. In these heterokaryons a factor which inhibits DNA synthesis in the cytotrophoblasts may inhibit DNA synthesis in JAr nuclei and at least be partly responsible for the inhibition of DNA synthesis observed.

Animals↗
PubMed1995

The imprinted H19 gene as a tumor marker in bladder carcinoma.

OBJECTIVES: Genomic imprinting is a newly discovered mechanism in genetics that is involved in tumorigenesis. H19 is an imprinted gene in the human, expressed from the maternal allele. It is extensively transcribed in fetal life but is not translated and functions as an RNA molecule. It has been suggested as a candidate tumor suppressor gene. We studied the expression of H19 in human cancer arising from tissues expressing H19 in fetal life, one of which is bladder mucosa. METHODS: In situ hybridization for H19 mRNA on paraffin sections of bladder carcinoma in different histologic grades. RESULTS: Low-grade (grade 1 of 3), noninvasive (Ta) papillary transitional cell bladder carcinoma did not express H19, but prominent expression was disclosed in higher grades, invasive transitional cell carcinomas (T1-T3/4). Expression was also evident in in situ bladder carcinoma (Tis), which tends to progress rapidly to invasive cancer. CONCLUSIONS: We suggest that H19 can be used as a tumor marker in human bladder carcinoma, where its expression indicates a more malignant potential.

Biomarkers, Tumor↗
PubMed1995

Down's syndrome as a model for the decisive role of maternal lineage in human evolution.

The study of human evolution and the mechanism of this process can be approached from physical anthropology, which examines phenotypic expression and molecular evolution, which investigates genotypic change. Alternatively, we suggest that human evolutional process can also be explained using present day examples of abberations in evolution. Thus, from both genotypic and phenotypic perspectives, we address the question of whether Down's syndrome is an instructive example to look into the decisive role of maternal lineage in human evolution.

Animals↗
PubMed1995

High maternal serum chorionic gonadotropin level in Downs' syndrome pregnancies is caused by elevation of both subunits messenger ribonucleic acid level in trophoblasts.

A unique product of human placenta is CG. Its concentration in maternal blood rises exponentially until 9-10 weeks' gestation, thereafter, it decreases to about 20% of the maximum, remaining constant from 16-17 until 40 weeks. High second-trimester maternal blood level indicates an increased risk for Downs' Syndrome (DS). This study's aim was to determine whether changes occur in the genetic expression of CG subunits in cultured trisomy-21 trophoblasts compared with various gestational age controls. Second-trimester trisomy-21 trophoblasts secrete 10 times more CG than gestational age-matched controls during the first day in culture: 878 (range, 235-2230) IU/g vs. 87 (range, 20-150) IU/g (P < 0.05). This high secretion closely resembles quantities secreted by first-trimester normal trophoblasts: 7500 (range, 3,850-10,000) IU/g. Both subunits' messenger RNA content are substantially increased, CG beta much more than CG alpha, although these genes are not located on chromosome 21. We conclude that at least one cause of high second-trimester maternal blood CG in DS pregnancies is a rise in alpha and beta CG messenger RNA levels in the trophoblast. We propose that at 12-14 weeks, when rapid decrease in maternal blood CG levels can be found, higher than normal values may indicate an increased risk for DS.

Cells, Cultured↗
PubMed1994

ABL and BCR genes are not imprinted in androgenetic and gynogenetic human tissues.

In the translocation leading to the formation of the Philadelphia chromosome, the hallmark of chronic myeloid leukemia (CML), the translocated chromosome 9 (ABL), is of paternal descent whereas chromosome 22 (BCR) is of maternal origin (1). To study possible imprinting of the human ABL and BCR genes, we used human tissues exclusively endowed with their maternally (benign teratoma) or paternally (complete hydatidiform mole) inherited chromosomes. Using the sensitive PCR technique followed by northern blotting, we demonstrate here that ABL and BCR are expressed to a similar extent in androgenetic and gynogenetic human tissues, thus suggesting that ABL and BCR genes are not imprinted in these human tissues.

Base Sequence↗
PubMed1994

Expression of the imprinted gene H19 in the human fetus.

The H19 gene is a parenterally imprinted maternally expressed gene which has a pivotal role in embryogenesis and fetal development. It is tightly linked to the IGF-II gene on chromosome 11p15.5 which is reciprocally imprinted. We studied the expression of the human H19 by in situ hybridization in an embryo 35 days post coitus (dpc) and in a fetus from the second trimester of pregnancy. The expression pattern of H19 in the human fetal tissues was similar to its expression in the mouse, and paralleled, with some exceptions, the expression of IGF-II in human fetuses. Abundant expression was found in organs comprising the fetoplacental unit: the placenta, the fetal adrenal, and liver. The expression in the fetal adrenal cortex was most prominent in the definitive cortex and somewhat weaker in the fetal zone. Considerable expression of H19 was found in the fetal liver as early as 35 dpc and in the second trimester. Hematopoietic cells in fetal liver did not express the gene. Moderate expression of H19 was detected in the epithelium of the small intestines, in endometrial stroma and Fallopian tube. In the kidney conspicuous labeling of the metanephric blastema was noted, which was markedly reduced with differentiation to tubules. This pattern of expression is identical to that of IGF-II in the fetal kidney and is relevant to the evolution of Wilms' tumor. No expression of H19 was found in the neural tube of the first trimester embryo or in the developing fetal brain in the second trimester, nor were transcripts detected in the choroid plexus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗