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Ch V Rao - One of the best experts on this subject based on the ideXlab platform.

  • presence of luteinizing hormone Human Chorionic Gonadotropin receptors in male breast tissues
    The Journal of Clinical Endocrinology and Metabolism, 2004
    Co-Authors: Harold E Carlson, Z M Lei, Philip Kane, Ch V Rao
    Abstract:

    Receptors for LH/Human Chorionic Gonadotropin (hCG) have been found in a variety of nongonadal tissues including the female breast. Using in situ hybridization and immunohistochemistry, we demonstrated the presence of LH/hCG receptor mRNA and protein in normal male breast tissue obtained at autopsy (n = 4) and archival samples of benign gynecomastia (n = 14) and male breast carcinoma (n = 5). Although the function of these receptors remains to be determined, the findings suggest the possibility that LH and hCG may play a role in the pathogenesis of male breast disorders.

  • Human fetal nongonadal tissues contain Human Chorionic Gonadotropin luteinizing hormone receptors
    The Journal of Clinical Endocrinology and Metabolism, 2004
    Co-Authors: M A Abdallah, Z M Lei, Natalie Greenwold, Steven T Nakajima, Eric Jauniaux, Ch V Rao
    Abstract:

    Human Chorionic Gonadotropin (hCG), a heterodimeric glycoprotein hormone produced in abundance by placental syncytiotrophoblasts, is preferentially secreted into maternal circulation. Fetal circulation also contains low levels of hCG that are probably derived from fetal kidney, liver, anterior pituitary gland, etc. In addition, the fetus has access to hCG present in exocoelomic and amniotic fluids. hCG has been found in a number of fetal tissues known to stimulate fetal adrenal and testicular steroidogenesis and is also thought to play a role in growth and differentiation of fetal tissues. This led us to test the hypothesis that fetal nongonadal tissues, as in the adult, may also contain hCG/LH receptors. This hypothesis was tested by immunocytochemistry, Western blotting, in situ hybridization, and RT-PCR. The results demonstrate that kidney, liver, pancreas, lung, small and large intestines, and adrenals contained hCG/LH receptors. Although the role of fetal nongonadal hCG/LH receptors is not known, they may mediate the pleiotropic actions of hCG in the growing Human fetus.

  • Human cervix contains functional luteinizing hormone Human Chorionic Gonadotropin receptors
    The Journal of Clinical Endocrinology and Metabolism, 2003
    Co-Authors: P C Lin, Z M Lei, Ch V Rao
    Abstract:

    The upper genital tract of women contains functional LH/Human Chorionic Gonadotropin (hCG) receptors. Whether the cervix, an anatomical continuum of the uterus and fallopian tubes, also contains these receptors has never been investigated. Multiple receptor detection techniques revealed their presence with higher levels in endocervix than in ectocervix. The receptor positive cells include stratified squamous luminal epithelium of the ectocervix, columnar epithelium, glands, blood vessels, and smooth muscle in the endocervix. Treatment of cervical tissue minces with hCG resulted in a significant increase in cAMP levels and a decrease in cyclooxygenase-2 protein levels in endocervix, but not in ectocervix. In summary, Human cervix contains functional LH/hCG receptors, which suggests that LH during the menstrual cycle and hCG during pregnancy may regulate cervical functions.

Anna Jankowska - One of the best experts on this subject based on the ideXlab platform.

  • Human Chorionic Gonadotropin beta subunit genes cgb1 and cgb2 are transcriptionally active in ovarian cancer
    International Journal of Molecular Sciences, 2013
    Co-Authors: Marta Kubiczak, Grzegorz P. Walkowiak, Ewa Nowakmarkwitz, Anna Jankowska
    Abstract:

    Human Chorionic Gonadotropin beta subunit (CGB) is a marker of pregnancy as well as trophoblastic and nontrophoblastic tumors. CGB is encoded by a cluster of six genes, of which type II genes (CGB3/9, 5 and 8) have been shown to be upregulated in relation to type I genes (CGB6/7) in both placentas and tumors. Recent studies revealed that CGB1 and CGB2, originally considered as pseudogenes, might also be active, however, the protein products of these genes have not yet been identified. Our study demonstrates the presence of CGB1 and CGB2 transcripts in ovarian carcinomas. While CGB1 and CGB2 gene activation was not detected in normal ovaries lacking cancerous development, our study demonstrates the presence of CGB1 and CGB2 transcripts in 41% of analyzed ovarian cancer cases.

  • coexpression of Human Chorionic Gonadotropin beta subunit and its receptor in nontrophoblastic gynecological cancer
    International Journal of Gynecological Cancer, 2008
    Co-Authors: Anna Jankowska, Miroslaw Andrusiewicz, Ewa Nowakmarkwitz, J Grabowski, Jerzy B Warchol
    Abstract:

    A considerable number of biochemical and physiologic studies evaluate the roles of Gonadotropins in carcinogenesis. Latest reports show that Human Chorionic Gonadotropin (hCG), and especially its beta subunit, are secreted by a variety of malignant tumors of different origin. However, the mechanism of hCG action and its role in tumor development is not known yet. This study, with the help of reverse transcription-polymerase chain reaction and immunohistochemistry, is an attempt to document the molecular presence of the hCGβ and luteinizing hormone/hCG receptor (LH/hCGR) in the ovarian, endometrial, and uterine cervix cancer tissues. The LH/hCGR, coexpressed with hCGβ, may act as a potential mediator of hCG action in nontrophoblastic gynecological cancers

  • reduction of Human Chorionic Gonadotropin beta subunit expression by modified u1 snrna caused apoptosis in cervical cancer cells
    Molecular Cancer, 2008
    Co-Authors: Anna Jankowska, Anna Szczerba, Beata Burczynska, Miroslaw Andrusiewicz, Artur Jarmolowski, Ewa Nowakmarkwitz, Samuel I Gunderson, Jerzy B Warchol
    Abstract:

    Secretion of Human Chorionic Gonadotropin, especially its beta subunit by malignant trophoblastic tumors and varieties of tumors of different origin is now well documented; however the role of hCG in tumorogenesis is still unknown. This study documents the molecular presence of Human Chorionic Gonadotropin beta subunit in uterine cervix cancer tissues and investigates a novel technique to reduce hCGβ levels based on expression of a modified U1 snRNA as a method to study the hormone's role in biology of Human cervical cancer cells cultured in vitro. The property of U1 snRNA to block the accumulation of specific RNA transcript when it binds to its donor sequence within the 3' terminal exon was used. The first 10 nucleotides of the Human U1 snRNA gene, which normally binds to the 5'ss in pre-mRNA were replaced by a sequence complementary to a 10-nt segment in the terminal exon of the hCGβ mRNA. Three different 5' end-mutated U1 snRNA expression plasmids were tested, each targeting a different sequence in the hCGβ mRNA, and we found each one blocked the expression of hCGβ in HeLa cells, a cervix carcinoma cell line, as shown by immunohistochemistry and qRT-PCR. Reduction of hCGβ levels resulted in a significantly increased apoptosis rate with almost 90% of cells transfected with modified anti-hCGβ U1 snRNAs showing morphological changes characteristic of the apoptotic process. These data suggest that Human Chorionic Gonadotropin beta subunit may act as a tumor growth-stimulating factor.

Laurence A Cole - One of the best experts on this subject based on the ideXlab platform.

  • hyperglycosylated Human Chorionic Gonadotropin and Human Chorionic Gonadotropin free beta subunit tumor markers and tumor promoters
    Journal of Reproductive Medicine, 2008
    Co-Authors: Laurence A Cole, Stephen A Butler
    Abstract:

    Human Chorionic Gonadotropin (hCG) is a heterogeneous glycoprotein hormone comprising an alpha-subunit and beta-subunit that can vary in peptide and carbohydrate structure. After conception, hCG produced by early trophoblast cells acts on luteinizing hormone (LH)/hCG receptor corpus luteum cells to promote progesterone production and establish maternal recognition of pregnancy. hCG is not simply 1 molecule, and 2 variants of hCG appear to have independent activities in promoting tumor cell growth, invasion and malignancy. Hyperglycosylated hCG (H-hCG), produced by cytotrophoblast cells, is a marker for cytotrophoblast cells and tumor marker for gestational trophoblastic diseases. H-hCG promotes growth and invasion in these cells during pregnancy implantation, and growth in varying degrees by many nontrophoblastic neoplasms. beta-hCG is a marker of poor prognosis shown to promote growth and invasion in vitro, suggesting autocrine growth factor properties. Vaccines to b-hCG have been successfully demonstrated, suggesting a potential adjuvant therapy in cancer treatment. Although sufficiently distinct in both structure and occurrence, similarities have been observed between H-hCG and beta-hCG as promoters of cell growth, invasion and malignancy. It is somewhat irregular for 2 structural variants of a molecule to have independent actions, actions very different to the gonadotropic function of the established hormone hCG.

  • hyperglycosylated Human Chorionic Gonadotropin and the source of pregnancy failures
    Fertility and Sterility, 2008
    Co-Authors: Yasushi Sasaki, Donald G Ladner, Laurence A Cole
    Abstract:

    Objective To investigate the proportion of hyperglycosylated Human Chorionic Gonadotropin (hCG-H) produced at the time of implantation as a predictor of pregnancy success. Design Measuring daily urine hCG and hCG-H on the day of implantation. The time of implantation was assumed to be the first day of hCG detection (total hCG >1 mIU/mL). Setting Urine samples were collected at volunteers' homes throughout city of Albuquerque. Patient(s) 110 women attempting to conceive spontaneously; 62 achieved pregnancies (42 to term and 20 failed). Intervention(s) None. Main Outcome Measure(s) Measurements of the total hCG and hCG-H, and calculations of the proportion of hCG-H. Result(s) In all 42 term pregnancies, the proportion of hCG-H on the day of implantation was >50%. This was also true for 7 of the 20 failures. Statistically significant lower proportions of hCG-H ( Conclusion(s) Hyperglycosylated is produced by cytotrophoblast cells in early pregnancy at the time of implantation. Effective proportions of hCG-H (>50%) are required for successful growth and invasion by cytotrophoblasts at the time of implantation. Low proportions of hCG-H at implantation predict failure and are likely to be the root of many pregnancy failures. The 7 of 20 failures with normal proportions of hCG-H were likely due to genetic, immune, or maternal causes. Measurement of a proportion of hCG-H

  • detection of perimenopause or postmenopause Human Chorionic Gonadotropin an unnecessary source of alarm
    American Journal of Obstetrics and Gynecology, 2008
    Co-Authors: Laurence A Cole, Sarah A Khanlian, Carolyn Y Muller
    Abstract:

    Objective The normal pituitary production of Human Chorionic Gonadotropin alongside luteinizing hormone, measurable in menopausal serum and urine was initially reported over 3 decades ago and has been described in numerous subsequent publications. Unfortunately, delays or cancellations of important medical procedures and use of needless chemotherapy still occurs because of the finding of Human Chorionic Gonadotropin in perimenopausal and postmenopausal woman. We describe the problem and a concise approach to this management dilemma in menopausal women. Study Design This is an outcomes study of 36 cases of perimenopausal and postmenopausal Human Chorionic Gonadotropin evaluated in cases referred to the USA hCG Reference Service. Results By report of the provided records, in 6 of 36 cases, unneeded chemotherapy was given for assumed recurrent gestational trophoblastic disease. In 9 cases, surgery was cancelled or postponed and in 3 cases renal transplantation was cancelled at the time of locating a matched donor kidney. In all cases the measured Human Chorionic Gonadotropin was due to menopausal production of pituitary Human Chorionic Gonadotropin. The average Human Chorionic Gonadotropin detected in perimenopausal cases was 6.4 ± 3.2 IU/L, and in postmenopausal cases was 11.6 ± 7.0 IU/L or significantly higher. In 24 cases, therapeutic doses of high-estrogen birth control pill were used to confirm pituitary origin with 23 cases demonstrating successful Human Chorionic Gonadotropin suppression. Conclusion Low levels of Human Chorionic Gonadotropin production in the perimenopausal and postmenopausal state is a normal physiologic phenomenon. Provider education is warranted and management protocols are suggested in all health-related fields to clarify the normality of low level pituitary Human Chorionic Gonadotropin production. Understanding this physiology will avoid delays in necessary therapies such as organ transplants, and will limit the misadventure of prescribing unnecessary treatments for presumed gestational malignancy.

  • Normal production of Human Chorionic Gonadotropin in menopause.
    The New England journal of medicine, 2007
    Co-Authors: Laurence A Cole, Yasushi Sasaki, Carolyn Y Muller
    Abstract:

    To the Editor: A positive test for the presence of Human Chorionic Gonadotropin (hCG) before menopause is an indication of pregnancy.1 A positive hCG test in menopausal women poses a diagnostic cha...

  • between method variation in Human Chorionic Gonadotropin test results
    Clinical Chemistry, 2004
    Co-Authors: Laurence A Cole, Jaime M Sutton, Trefor Higgins, George S Cembrowski
    Abstract:

    Background: Results on sera and calibrators vary 1.4- to 2.3-fold among commercial Human Chorionic Gonadotropin (hCG) assays. The relative contributions of calibrators, standards, hCG charge isoforms, and major structural variants to this variation have not been quantified. Methods: Purified hCG was separated by isoelectric focusing into four fractions with pI ranges of 3–4, 4–5, 5–6, and 6–7. These four fractions together with pure hCG, hyperglycosylated hCG, hCG β-subunit (hCGb), nicked hCG, and hCGb core fragment (hCGbcf) were tested in nine commonly used commercial serum assays for hCG. The compositions of pure hCG preparations, standards, and commercial hCG preparations were determined by immunoassay. Results: The three pure hCG preparations and the four hCG charge isoforms each showed parallel responses in the nine commercial hCG assays. Although wide variations were found in the detection of hCG structural variants by the nine assays (range for hyperglycosylated hCG, 468-1544 IU/L; for hCGb, 3187-5535 IU/L; for nicked hCG, 2736-4240 IU/L; and for hCGbcf, <2–130 IU/L), this did not correlate with the between-method variation observed in results for the three pure hCG preparations. Commercial preparations of hCG and calibrators showed great variation in their content of hCG structural variants (from 34% to 100% intact hCG). Conclusions: Intermethod differences in hCG results were not explained by changes in responses attributable to hCG charge isoforms or to hCG structural variants, but wide variation was observed in concentrations of hCG structural variants in calibrators and in detection of these structural variants. Differences in assay specificity and in composition of the calibrators are the most likely sources of between-method variation.

Jerzy B Warchol - One of the best experts on this subject based on the ideXlab platform.

  • coexpression of Human Chorionic Gonadotropin beta subunit and its receptor in nontrophoblastic gynecological cancer
    International Journal of Gynecological Cancer, 2008
    Co-Authors: Anna Jankowska, Miroslaw Andrusiewicz, Ewa Nowakmarkwitz, J Grabowski, Jerzy B Warchol
    Abstract:

    A considerable number of biochemical and physiologic studies evaluate the roles of Gonadotropins in carcinogenesis. Latest reports show that Human Chorionic Gonadotropin (hCG), and especially its beta subunit, are secreted by a variety of malignant tumors of different origin. However, the mechanism of hCG action and its role in tumor development is not known yet. This study, with the help of reverse transcription-polymerase chain reaction and immunohistochemistry, is an attempt to document the molecular presence of the hCGβ and luteinizing hormone/hCG receptor (LH/hCGR) in the ovarian, endometrial, and uterine cervix cancer tissues. The LH/hCGR, coexpressed with hCGβ, may act as a potential mediator of hCG action in nontrophoblastic gynecological cancers

  • reduction of Human Chorionic Gonadotropin beta subunit expression by modified u1 snrna caused apoptosis in cervical cancer cells
    Molecular Cancer, 2008
    Co-Authors: Anna Jankowska, Anna Szczerba, Beata Burczynska, Miroslaw Andrusiewicz, Artur Jarmolowski, Ewa Nowakmarkwitz, Samuel I Gunderson, Jerzy B Warchol
    Abstract:

    Secretion of Human Chorionic Gonadotropin, especially its beta subunit by malignant trophoblastic tumors and varieties of tumors of different origin is now well documented; however the role of hCG in tumorogenesis is still unknown. This study documents the molecular presence of Human Chorionic Gonadotropin beta subunit in uterine cervix cancer tissues and investigates a novel technique to reduce hCGβ levels based on expression of a modified U1 snRNA as a method to study the hormone's role in biology of Human cervical cancer cells cultured in vitro. The property of U1 snRNA to block the accumulation of specific RNA transcript when it binds to its donor sequence within the 3' terminal exon was used. The first 10 nucleotides of the Human U1 snRNA gene, which normally binds to the 5'ss in pre-mRNA were replaced by a sequence complementary to a 10-nt segment in the terminal exon of the hCGβ mRNA. Three different 5' end-mutated U1 snRNA expression plasmids were tested, each targeting a different sequence in the hCGβ mRNA, and we found each one blocked the expression of hCGβ in HeLa cells, a cervix carcinoma cell line, as shown by immunohistochemistry and qRT-PCR. Reduction of hCGβ levels resulted in a significantly increased apoptosis rate with almost 90% of cells transfected with modified anti-hCGβ U1 snRNAs showing morphological changes characteristic of the apoptotic process. These data suggest that Human Chorionic Gonadotropin beta subunit may act as a tumor growth-stimulating factor.

Kristina Hotakainen - One of the best experts on this subject based on the ideXlab platform.

  • tumor expression of Human Chorionic Gonadotropin beta mrna and prognosis of prostate cancer treated by radical prostatectomy
    Scandinavian Journal of Clinical & Laboratory Investigation, 2019
    Co-Authors: Susanna Lintula, Ulfhakan Stenman, Tuomas Mirtti, Antti Rannikko, Anna Butzow, Anna Lempiainen, Jakob Stenman, Kristina Hotakainen
    Abstract:

    AbstractThe beta subunit of Human Chorionic Gonadotropin (hCGβ) is encoded by six genes (CGB) classified as type I and type II. CGB mRNA is produced in large amounts by trophoblastic tissues and in...

  • overexpression of Human Chorionic Gonadotropin β genes 3 5 and 8 in tumor tissue and urinary cells of bladder cancer patients
    Tumor Biology, 2007
    Co-Authors: Kristina Hotakainen, Annukka Paju, Susanna Lintula, Jakob Stenman, Riikka Jarvinen, Erkki Rintala, Ulfhakan Stenman
    Abstract:

    Objective: Human Chorionic Gonadotropin (hCG) is a marker of trophoblastic tumors, and the serum concentration of the free β-subunit (hCGβ) is an independent prognostic marker in se

  • Human Chorionic Gonadotropin in cancer
    Clinical Biochemistry, 2004
    Co-Authors: Ulfhakan Stenman, Henrik Alfthan, Kristina Hotakainen
    Abstract:

    Abstract Human Chorionic Gonadotropin (hCG) is mainly used for detection and monitoring of pregnancy and pregnancy-related disorders but it is also an extremely sensitive and specific marker for trophoblastic tumors of placental and germ cell origin. Thus treatment of relapsing choriocarcinomas and testicular germ cell tumors is often initiated on the basis of rising hCG levels even in the absence of clinical or histological evidence of a relapse. While these tumors mostly produce the intact heterodimeric hormone consisting of an α (hCGα), and a β subunit (hCGβ), many nontrophoblastic tumors produce only hCGβ This is usually a sign of aggressive disease and elevated serum levels of hCGβ are strongly associated with poor prognosis. Elevated serum levels are observed in 45–60% of patients with biliary and pancreatic cancer and in 10–30% of most other cancers. Methods that detect hCG and hCGβ together are mainly used for measurement of hCG-like immunoreactivity in serum. However, the reference range for hCG is 5–8 fold higher than that for hCGβ and thus moderately elevated levels can be identified only with a specific and sensitive hCGβ assay.

  • the free beta subunit of Human Chorionic Gonadotropin as a prognostic factor in renal cell carcinoma
    British Journal of Cancer, 2002
    Co-Authors: Kristina Hotakainen, Borje Ljungberg, Annukka Paju, Torgny Rasmuson, Henrik Alfthan, U H Stenman
    Abstract:

    The free β-subunit of Human Chorionic Gonadotropin β is expressed in several nontrophoblastic tumours and this is usually associated with aggressive disease. Little is known about Human Chorionic Gonadotropin β expression in renal cancer. We determined the pretreatment levels of Human Chorionic Gonadotropin β in serum of patients with renal cell carcinoma, and studied whether elevated levels predicted the clinical outcome. Serum samples were collected before surgery from 177 patients with renal cell carcinoma and from 84 apparently healthy controls. Human Chorionic Gonadotropin β in serum was measured by a highly sensitive time-resolved immunofluorometric assay. The prognostic value of Human Chorionic Gonadotropin β, and of usual clinical and pathological variables was analyzed by the Kaplan-Meier method, the log rank test and Cox multiple hazard regression. The serum concentrations of Human Chorionic Gonadotropin β were increased in 23% of the renal cell carcinoma patients and they were significantly higher in patients with renal cell carcinoma than in controls (P<0.0001). The concentrations did not correlate with clinical stage and histopathological grade, but patients with increased Human Chorionic Gonadotropin β levels had significantly shorter survival time than those with levels below the median (cut-off 1.2 pmol l−1, P=0.0029). In multivariate analysis Human Chorionic Gonadotropin β, tumour stage and grade were independent prognostic variables. The serum concentration of Human Chorionic Gonadotropin β is an independent prognostic variable in renal cell carcinoma. The preoperative value of Human Chorionic Gonadotropin β in serum may be used to identify patents with increased risk of progressive disease.