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PubMed1987

Expectant management of presumed ectopic pregnancies.

Thirteen patients with presumed diagnosis of unruptured ectopic pregnancy underwent expectant management. The diagnosis was based on the criteria of clinical stability, no intrauterine gestation sac by sonogram, and falling beta subunit human chorionic gonadotropin titer. The diagnosis also was based on no gross evidence of trophoblastic tissue on sharp curettage and alteration in uterotubal anatomy at laparoscopy. In these 13 patients, titers continued to drop and were below assay detectability (1.5 miu/ml) by 1 to 5 weeks. Only one patient required a laparotomy. Hysterosalpingograms in ten of the patients showed normal, patent tubes in seven. One patient had cornual occlusion and two showed a hydrosalpinx with spillage. A second laparoscopy in seven patients demonstrated normal tubes in all but one. At present, three patients have delivered term infants and two have had first trimester spontaneous abortions. These observations suggest that expectant management of tubal pregnancies is appropriate under rigidly controlled conditions.

Adolescent↗

PubMed1986

Carcinoembryonic antigen staining in choriocarcinoma.

Choriocarcinoma of the colon presented as life-threatening lower gastrointestinal bleeding and a pathologic femoral fracture in a 42-year-old man. Elevated serum carcinoembryonic antigen (CEA) levels and immunohistochemical positivity for CEA in neoplastic syncytiotrophoblasts were noted, as well as the expected positivity for the beta subunit of human chorionic gonadotropin (beta HCG). Additional cases, including one of two gestational choriocarcinomas and one of four testicular choriocarcinomas studied immunocytochemically for CEA also demonstrated positivity. Although CEA staining is commonly associated with tumors derived from the surface epithelium of the gastrointestinal tract and other organs, its presence in choriocarcinomas should not be interpreted as conclusive evidence of primary origin from these sites.

Adult↗

PubMed1993

Malignant trophoblastic tumors: immunohistochemical and flow cytometric comparison of choriocarcinoma and placental site trophoblastic tumors.

We performed an immunohistochemical and flow cytometric study of the formalin-fixed, paraffin-embedded tissues of eight recent gestational choriocarcinomas (CCs) and three placental-site trophoblastic tumors (PSTTs). The follow-up period ranged from 1 to 144 months (mean, 74.3 months). In the CCs, which consisted predominantly of cytotrophoblasts and syncytiotrophoblasts intermingled with small amounts of intermediate trophoblasts, cytotrophoblasts were occasionally positive for beta-subunit human chorionic gonadotropin (HCG) and syncytiotrophoblasts contained abundant HCG. Some intermediate trophoblasts were positive for HCG and many were positive for human placental lactogen. In the three PSTTs, which were characterized by a monomorphic proliferation of intermediate trophoblasts, the tumor cells were positive for human placental lactogen and placental alkaline phosphatase. The tumors of two patients, including one fatal case, contained more human placental lactogen-positive cells than HCG-positive cells, while the tumor of the remaining patient, who had high serum HCG levels, showed a reversed staining pattern resembling that of CC; this patient has been alive without disease for 9 years. One CC patient and one PSTT patient died of multiple lung metastases, despite hysterectomy and multiagent chemotherapy. All CCs and PSTTs had an exclusively diploid DNA content, and there was no correlation among histopathologic and immunohistochemical features, DNA ploidy, S-phase fraction, and clinical outcome for patients with these tumors. These results suggest that there is a PSTT that immunohistochemically resembles CC and that flow cytometric and immunohistochemical analysis may not be effective tools to predict the biologic behavior of malignant trophoblastic tumors.

Adult↗

PubMed1984

Correlation of plasma hormone levels and peripheral circulating lymphocyte subpopulations during human pregnancy.

Using monoclonal antibodies (OKT3, OKT4, OKT8) peripheral blood lymphocyte subsets were determined in 40 normal primiparous pregnant women and compared with those of 31 nonpregnant controls. In pregnant women plasma concentrations of estradiol, progesterone, human placental lactogen (HPL), beta subunit of human chorionic gonadotropin (beta HCG), and alpha-fetoprotein were measured by means of radioimmunoassay. We studied if correlations between peripheral lymphocyte subsets and plasma hormone levels might exist. We observed in pregnant women from 10 to 40 wk of amenorrhea a decrease in the percentage of OKT3 and OKT8 cells, and during the course of pregnancy an increase in the percentage of OKT4 cells. This increase inversely correlated with plasma beta HCG levels and directly correlated with plasma HPL levels.

Adult↗

PubMed1997

Oral immunization with recombinant vaccina expressing cell-surface-anchored beta hCG induces anti-hCG antibodies and T-cell proliferative response in rats.

A vaccinia recombinant, VSS2, expressing cell-surface-anchored beta-subunit of human chorionic gonadotropin (beta hCG) has earlier been found to induce high titered anti-hCG antibodies in rats immunized by tail scarification. The immunogenicity of this recombinant was compared in rats which received the virus through different routes of inoculation: intradermal, intragastric, intrajejunal or by tail scarification. The recombinant virus induced high titers of anti-hCG antibodies in all instances although the titers were about one log lower when the recombinant virus was delivered orally. The recombinant was found to induce T-cell proliferative response in rats of all immunization groups.

Animals↗

PubMed2003

A central role for Ets-2 in the transcriptional regulation and cyclic adenosine 5'-monophosphate responsiveness of the human chorionic gonadotropin-beta subunit gene.

Ets-2 has an important role in controlling the differentiation of the placenta. Here we show by truncation and mutational analysis that two closely spaced Ets-2 binding sites in the proximal promoter of the human chorionic gonadotropin beta5 (hCGbeta5) gene constitute a major enhancer for hCGbeta gene expression in JAr and JEG-3 human choriocarcinoma cells and in mouse NIH3T3 cells. Contrary to a previous report, we also demonstrate that the ability of Ets-2 to enhance transcription is subject to control by the Ras/MAPK pathway, although this relationship is less easily demonstrable in JAr and JEG-3 choriocarcinoma cells than in the 3T3 cells because the former already possess a fully activated MAPK pathway and contain Ets-2 phosphorylated at threonine residue at T72. Coexpression of Ets-2 and activated Ras in 3T3 cells led to activation of MAPK/ERK kinase 1/2, phosphorylation of Ets-2 at T72, and an approximately 120-fold up-regulation of reporter gene expression from a short (-175) hCGbeta promoter. Fold activation in JAr and JEG-3 cells was rather less (20- to 30-fold), but basal activity was much higher. These effects on promoter activity were largely reversed in presence of the MAPK inhibitor PD98059, which prevents ERK1/2 activation, and partially reversed by mutating T72 on Ets-2. We finally show that the ability of 8-bromoadenosine-cAMP to stimulate hCGbeta promoter activity in JAr and JEG-3 cells occurs with a short promoter lacking the upstream elements previously considered to be essential for cAMP activation of the gene and, through mutational analysis, confirm that the major cAMP effects on the hCGbeta promoter are mediated through the proximal Ets-2 enhancer. The data are consistent with the hypothesis that Ets-2 has a general and possibly essential role in controlling the activity of genes associated with trophectoderm differentiation.

3T3 Cells↗

PubMed1997

Recombinant adenovirus synthesizing cell surface-anchored beta hCG induces bioneutralizing antibodies in rats.

A recombinant adenovirus (re-Ad) has been constructed that synthesizes a cell surface-anchored form of the beta-subunit of human chorionic gonadotropin (beta hCG). This was achieved by in-frame fusion of beta hCG cDNA at its C terminus with the gene sequences coding for the vesicular stomatitis virus glycoprotein (VSVg) transmembrane domain. The fusion protein gene was placed under the control of human cytomegalovirus (hCMV) immediate early promoter and this expression cassette was inserted into the E1 region of Ad type 5 by homologous recombination. In vitro experiments using re-Ad-infected 293 cells showed that beta hCG fusion protein was made as early as 6 h post infection and the protein was anchored to the cell membrane as seen by immunofluorescence staining. The re-Ad induced bioneutralizing antibodies (Ab) to hCG when inoculated in rats through intraperitoneal or intramuscular routes. The Ab were made in a dose-dependent manner. However, orally delivered re-Ad failed to generate any significant immune response.

Adenoviridae↗

PubMed1995

Influence of codon usage and translational initiation codon context in the AcNPV-based expression system: computer analysis using homologous and heterologous genes.

Codon usage by all the known gene sequences from Autographa californica nuclear polyhedrosis virus (AcNPV) was compared with that of firefly luciferase (luc) and the beta subunit of human chorionic gonadotropin (beta hCG) expressed to contrasting levels in the baculovirus system. The highly expressed luc gene showed a codon usage similar to AcNPV genes, as reflected by a very low D-squared statistic value (0.78) and a similar G/C usage (45%) at wobble positions. However, the underexpressed beta hCG gene displayed a high D-squared value (7.3) and G/C usage (82.5%) at the wobble base position. Alignment of the 20 nucleotides around the initiation codon of 23 AcNPV genes identified a novel consensus translation initiation sequence aag/ta/tat/aa/cAAaATGaa/ct/ag/aAan, which was quite different from the Kozak consensus sequence (GCC)GCCA/GCCATGG. An extension of these analyses to a sample of other heterologous genes overexpressed and underexpressed in BEVS suggested similar trends. These theoretical analyses have important implications for heterologous gene expression in this system.

Animals↗

PubMed1993

The measurement of urinary beta core fragment in conjunction with serum CA125 does not aid the differentiation of malignant from benign pelvic masses.

The urinary concentration of the renal metabolite of the beta subunit of human chorionic gonadotropin (beta core) has been proposed as a tumor marker in certain nontrophoblastic malignancies including those of the female genital tract. A previous study investigated the use of urinary beta core in conjunction with serum CA125 in distinguishing malignant from benign pelvic masses and showed that the combined test improved the overall sensitivity to 88%; this was greater than that for either test alone. However, the cutoff levels used to distinguish normal from abnormal were approximately six times greater than those generally used for CA125 and four to five times lower than those used for beta core in our laboratory. Furthermore there was no recognition of the possible difference in normal levels of beta core between pre- and postmenopausal women. We have examined a similar group of cases using our cutoff levels for urinary beta core of 0.36 ng/ml in premenopausal women and 0.48 ng/ml in postmenopausal women and 35 u/ml for CA125. We show that measurement of CA125 is substantially more sensitive that that of beta core and that the combination of beta core with CA125 does not improve the overall sensitivity of the test. However, there was a small improvement in positive predictive value if both tests were positive (97.5%) and of specificity when one or the other test was negative (98.5%).

Adult↗

PubMed1995

Transcriptional regulation of cell line-dependent, baculovirus-mediated expression of foreign genes.

Cell line-dependent expression of foreign genes in the baculovirus system was investigated using a recombinant vAc beta hCG-luc virus carrying two reporter genes--beta subunit of human chorionic gonadotropin (beta hCG) and luciferase (luc)--placed under the transcriptional control of the Autographa californica nuclear polyhedrosis virus (AcNPV) polyhedrin gene promoters. Five different lepidopteran cell lines derived from Spodoptera frugiperda (Sf21 and Sf9), Bombyx mori (BmN and Bm5), and Trichoplusia ni (TN368) were used as host cells. TN368 expressed both beta hCG and LUC to maximum levels, followed by BmN, Sf21, and Sf9 in descending order. Bm5 did not show any evidence of synthesis of the two proteins. Dot blot analysis of DNA from the vAc beta hCG-luc-infected cells revealed that the level of entry of viral DNA was the same for all the five cell lines. After the completion of viral DNA replication (18 hr post infection), the level of viral DNA was the same for all the cell lines except for Bm5 where viral DNA replication did not take place and the residual virus was cleared from the cells. Analysis of RNA from the four expressing cell lines revealed a direct correlation between protein levels and levels of mRNA, suggesting transcriptional control. Differences in mRNA stability between cell lines was also evident. Gel retardation analysis of a host factor binding to transcriptionally important sequence motifs within the AcNPV polyhedrin gene promoter revealed an inverse correlation between the levels of this polyhedrin promoter-binding protein (PPBP) and reporter gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Cancer antigen 125, tissue polypeptide antigen, carcinoembryonic antigen, and beta-chain human chorionic gonadotropin as serum markers of epithelial ovarian carcinoma.

Cancer antigen 125 (CA 125) is common to most epithelial ovarian tumors. Therefore, it is potentially a good marker of this disease. This hypothesis was evaluated by measuring the serum levels of CA 125 in 81 patients with ovarian cancer (25 with nonactive and 56 with active disease), in 105 patients of both sexes with nonovarian tumors, and in 171 healthy controls of both sexes. The serum levels of three other markers, tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), and human chorionic gonadotropin, beta subunit (beta-hCG), were also measured in the same 357 subjects. The results of this study clearly indicate the clinical irrelevance of both CEA and beta-hCG as tumor markers in ovarian carcinomas. Conversely, the clinical usefulness of CA 125 and TPA was confirmed. In particular, CA 125 and TPA showed comparable sensitivity, while CA 125 showed a higher specificity for ovarian cancer than TPA. The association of CA 125 with TPA was very useful in continuous observation of patients with active disease in order to evaluate the clinical effectiveness of the therapy. Moreover, for patients in clinical remission, the markers allowed early detection of a recurrence of the disease.

Adult↗

PubMed1988

Extragonadal germ cell tumors. Clinicopathologic findings and treatment experience in 12 patients.

In patients with primary germ cell tumors, treatment with combination chemotherapy followed by surgical debulking of residual tissue usually produces favorable results. The best treatment for patients with extragonadal germ cell tumors (EGCT) remains a problem. In our series of 12 patients, important clinical features were related to the site of bulky tumor, and all patients exhibited sharply elevated levels of lactate dehydrogenase (LDH), beta subunit human chorionic gonadotropin (beta-HCG), and/or alpha-fetoprotein (AFP). Each patient was treated with systemic chemotherapy, and ten were treated with the same combination chemotherapy--cyclophosphamide, actinomycin, vinblastine, bleomycin, and cisplatin (VAB) alternating with VP-16 and vincristine (VV). Of these ten patients, five died of progressive disease, three of whom had brain metastases. The other five are alive and clinically free of disease. The addition of VP-16 and vincristine did not improve responses. Advanced disease at presentation contributes to the poorer prognosis for these patients. Earlier diagnosis and surgical debulking may improve the long-term survival of patients with this disease.

Adult↗

PubMed1987

The immune response to a synthetic peptide analogous to the 109-145 beta hCG carboxyl-terminus is directed against two major and two minor regions.

The immune response to a 37-amino acid synthetic peptide analogous to the carboxyl-terminal part (109-145) of the human chorionic gonadotropin beta subunit (beta hCG) was studied with monoclonal antibodies selected from 31 cell fusion experiments. Analysis of the immunogenic determinants borne on the synthetic peptide (CTP) showed a prevailing response to two immunodominant regions. The first was located on the 110-116 amino acid sequence of the CTP which is also the most hydrophilic region: 50% of anti-CTP antibodies selected for their high binding to 125I beta hCG were directed to this sequence. A second immunodominant portion was recognized by four antibodies, and comprised amino acids 134 to 139, representing a highly O-glycosylated region on the native protein. Moreover, a unique antibody designated FB13 bound to a region located on the last seven amino acids (139-145) of beta hCG. Finally, a hypothetical conformational determinant was recognized by antibody FB02 within the 121-145 region. Thus, the immune response to CTP was directed against two major and two minor regions. These antigenic determinants were demonstrated to be accessible for antibody binding on both the hCG molecule and its beta subunit. Localization of these epitopes suggests a relationship between the hydrophilicity and the immunological potency of different CTP regions.

Amino Acid Sequence↗

PubMed2005

A tumor in the medulla oblongata producing beta-HCG and AFP.

A 23 year-old woman presented with dysarthria, hoarseness, dysphasia, ataxia and dyspnoea. MRI showed a mass of heterogeneous intensity at the dorsal medulla oblongata. Laboratory studies revealed high serum alpha-fetoprotein (AFP) and beta-subunit human chorionic gonadotropin (beta-HCG) levels. No other tumours were found on systemic investigation. An intracranial non-germinomatous germ cell tumour (NGGCT) was strongly suspected. The patient received combination chemotherapy using ifosfamide, cisplatin, and etoposide and local irradiation to a total of 52 Gy. Serum AFP and beta-HCG levels normalized after four cycles of chemotherapy and she became asymptomatic apart from mild postural hypotension. A follow-up MRI showed only a tiny residual lesion in the medulla oblongata, which has been stable for more than three years. Surgical resection should be carefully considered in patients with brainstem tumours with elevation of serum tumour markers as chemo- and radiotherapy may be effective for brainstem NGGCT.

Adult↗

PubMed2005

Differential gene expression identified in complete hydatidiform mole by combining suppression subtractive hybridization and cDNA microarray.

Complete hydatidiform mole (CHM) is a type of gestational trophoblastic disease with pure paternal chromosome contribution and unpredictable malignant potential. As an attempt to assess the molecular pathogenesis of CHM, suppression subtractive hybridization (SSH) combined with cDNA microarray was used to compare the gene expression pattern of CHM compared with normal first-trimester placenta of similar gestational ages. cDNA microarray analysis using tissue-specific chips constructed with subtracted cDNA libraries identified 13 differentially expressed gene transcripts. Quantitative real-time polymerase chain reaction (PCR) confirmed up-regulation of human chorionic gonadotropin beta subunit (CGB) (P=0.0008) and KIAA1200 (P=0.0005), a G-protein regulator, as well as down-regulation of osteopontin (SPP1) (P<0.0001) in 14 genotyped CHM when compared with 15 normal placentas. These candidate genes may contribute toward understanding the mechanism involved with the development and progression of CHM.

Adult↗

PubMed2000

Metastatic spinal intramedullary germinoma with elevated cerebrospinal fluid chorionic gonadotropin: a case report.

We treated a patient whose unusual recurrent germinoma illustrates the diagnostic value of measuring human chorionic gonadotropin beta subunit (HCG-beta) in cerebrospinal fluid (CSF) and serum. A 25-year-old man with a suprasellar germinoma and ventricular dissemination was treated successfully with systemic chemotherapy and cranial irradiation. Six years later he developed progressive numbness and weakness in both upper extremities. Magnetic resonance imaging (MRI) disclosed an intramedullary spinal cord tumor in the cervical region. The CSF concentration of HCG-beta was elevated and exceeded that in serum. After completion of systemic chemotherapy and spinal irradiation, symptoms subsided and the tumor was no longer evident on MRI. Based on the patient's history and the rapid response of the tumor to treatment, the spinal cord tumor was considered a metastatic intramedullary spinal germinoma representing CSF dissemination via the central canal.

Adult↗

PubMed2006

[Construction and immunogenicity of hCG chimeric peptides (CP1 and CP10) containing three self- B cell epitopes and six foreign T cell epitopes].

Two bio-synthesizing chimeric peptide (CP) immunogens named CP1 and CP10 have been designed, which consist of three linear B cell epitopes (BCE) of human chorionic gonadotropin beta subunit (beta-hCG) and six foreign T cell epitopes including two "promiscuous" TCEs from hepatitis B surface antigen and tetanus toxoid. Two artificial genes encoding CP1 and its derivative CP10 were synthesized, which could be expressed in E. coli at the level of about 1% of the total cell proteins when inserted into the thermo-induction vector respectively. In Western blot tests, the expressed CP1 and CP10 proteins with about 16.5 kD shown on the SDS-polyacrylamide gel electrophoresis (PAGE) gel can be recognized by the monoclonal or polyclonal antibodies specific to each linear epitope of beta-hCG. Each of expressed proteins can be purified with 95% relative homogeneity using our improved method of preparative gel PAGE. Their yields were about 1-2 mg per 12 L culture. Also, the CPl and CP10 immunogens can induce antibodies in mice that recognize recombinant CP1 betar CP10 and natural beta-hCG, and there are three anti-beta5, beta9 and beta8 BCE antibodies in their antisera. The construction and expression of beta-hCG CP1 and CP10 will provide new immunogens for developing an ideal and superior hCG birth control and/or tumor therapeutic vaccine.

Animals↗

PubMedDate not supplied

[Chorionic gonadotropin (beta-HCG) in the amniotic fluid in normal pregnant women].

Human chorionic gonadotropin beta subunit (beta-HCG) was measured in amniotic fluid and radioimmunoassay levels compared with those obtained in plasma from normal pregnant women. Amniotic beta-HCG exhibited a secretory pattern similar to that seen in the plasma compartment. Nonetheless amniotic beta-HCG had an elevation peak later than its plasma counterpart, with a progressive decrease that persisted throughout gestation without reaching a nadir as it occurred in plasma. Such a pattern of HCG production contained in the amnion is compatible with an HCG conformation released by the syncytiotrophoblast.

Amniotic Fluid↗