scholarly journals Siglec-6 is expressed in gestational trophoblastic disease and affects proliferation, apoptosis and invasion

2012 ◽  
Vol 19 (6) ◽  
pp. 827-840 ◽  
Author(s):  
Kristen K Rumer ◽  
Miriam D Post ◽  
Rhea S Larivee ◽  
Martina Zink ◽  
Jill Uyenishi ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Reproductive Tract ◽  
Expression Patterns ◽  
Peptide Hormone ◽  
Gestational Trophoblastic Disease ◽  
Diagnostic Utility ◽  
Dependent Manner ◽  
Independent Manner ◽  
Functional Studies ◽  
Trophoblastic Disease

Sialic acid immunoglobulin-like lectin (Siglec)-6 is a transmembrane receptor that binds leptin. Leptin is an obesity-associated peptide hormone overexpressed in gestational trophoblastic disease (GTD). GTD encompasses several placental abnormalities that range from benign to malignant. Among GTD, molar placentas are characterized by excess proliferation, whereas gestational trophoblastic neoplasias (GTN) have characteristically aggressive invasion. We hypothesized that in GTD, Siglec-6 expression would increase with disease severity and that Siglec-6 and leptin would promote proliferation, inhibit apoptosis and/or promote invasion. Siglec-6 expression patterns were evaluated with particular attention to the diagnostic utility of Siglec-6 in GTD (controls: normal placentas (n=32), hydropic abortus placentas (n=7), non-GTD reproductive tract cancers (n=2); GTD: partial moles (PM; n=11), complete moles (n=24), GTN (n=6)). In normal placentas, Siglec-6 expression dramatically decreased after 8 weeks gestation. Complete molar placentas had significantly higher Siglec-6 expression than controls, but expression was not significantly different from PM. In GTN, Siglec-6 expression was low. These data suggest that Siglec-6 may have diagnostic utility for distinguishing complete moles from normal and hydropic abortus placentas. Functional studies in choriocarcinoma-derived BeWO cells demonstrated a complex interplay between Siglec-6 expression and leptin exposure. In cells lacking Siglec-6, leptin treatment promoted invasion, likely through interaction with LepR leptin receptor, without affecting proliferation or apoptosis. Siglec-6 expression promoted proliferation in a leptin-dependent manner, but protected cells from apoptosis and promoted invasion in a leptin-independent manner. We propose that Siglec-6 and leptin play a role in the aberrant properties characteristic of GTD, namely excess proliferation and invasion.

A Novel Tetrameric Venom Protein, Agglucetin from Agkistrodon acutus , Acts as a Glycoprotein Ib Agonist

2001 ◽  
Vol 86 (10) ◽  
pp. 1077-1086 ◽  
Author(s):  
Wen-Jeng Wang ◽  
Tur-Fu Huang
Keyword(s):  
Flow Cytometric Analysis ◽  
Inhibitory Effect ◽  
Ionization Mass ◽  
Dependent Manner ◽  
Independent Manner ◽  
Venom Protein ◽  
Functional Studies ◽  
Reducing Conditions ◽  
Intracellular Ca ◽  
Von Willebrand

SummaryA novel platelet agglutination inducer, agglucetin, was purified from the Formosan Agkistrodon acutus snake venom. It migrated as a single band with an apparent molecular mass of 58.8 kDa and two distinct bands of 16.2/14.5 kDa under non-reducing and reducing conditions by SDS-PAGE, respectively. Further confirmed by FPLC, electrospray ionization mass spectrometry and 2D-PAGE, native agglucetin exists as a tetramer composed of disulfide-linked α1, α2, β1 and β2 subunits. Partial N-terminal sequence of agglucetin subunit showed a high degree of homology to those of C-type lectin-like glycoprotein (GP) Ib binding proteins. Functional studies showed that agglucetin, in the absence of von Willebrand factor (vWF), dose-dependently induced platelet agglutination and caused a negligible elevation of intracellular Ca+2 mobilization and thromboxane B2 formation in human platelet suspensions. Anti-GP Ib monoclonal antibodies (mAbs), AP1 or LJ-Ib1, specifically inhibited agglucetin-induced platelet agglutination in a dose-dependent manner. However, EDTA, arietin (a long chain RGD-containing disintegrin), 7E3 (an anti-GP IIb/IIIa mAb), heparin, hirudin, PGE1, or indomethacin exhibited no inhibitory effect on agglucetin-induced platelet agglutination. Furthermore, flow cytometric analysis revealed that FITC-agglucetin dose-dependently bound to human formalin-fixed platelets in a saturable manner, and its binding was specifically blocked by anti-GP Ib mAb. It is concluded that agglucetin, acts specifically on an epitope of platelet membrane GP Ib overlapping with that of AP1, causing platelet agglutination in a Ca+2- and GP IIb/IIIa-independent manner.

scholarly journals Coexpression of SFRP1 and WIF1 as a Prognostic Predictor of Favorable Outcomes in Patients with Colorectal Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Shiyong Huang ◽  
XiaoMing Zhong ◽  
Jun Gao ◽  
Rongfeng Song ◽  
Hongyu Wu ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Wnt Signaling Pathway ◽  
Gene Mutations ◽  
Tnm Stage ◽  
Dependent Manner ◽  
Independent Manner ◽  
Colorectal Tumorigenesis ◽  
Prognostic Predictor ◽  
Multivariate Survival Model ◽  
Wnt Inhibitory Factor 1

Colorectal tumorigenesis is ascribed to the activity of Wnt signaling pathway in a ligand-independent manner mainly through APC and CTNNB1 gene mutations and in a ligand-dependent manner through low expression of Wnt inhibitors such as WNT inhibitory factor 1 (WIF1) and secreted frizzled related protein 1 (SFRP1). In this study we found that WIF1 protein expression was increased and SFRP1 was decreased significantly in CRC tissue versus normal tissue, and high expression of WIF1 was associated with big tumor diameters and deep invasion, and loss of SFRP1 expression was associated with the left lesion site, deep invasion, and high TNM stage. Among the four expression patterns (WIF+/SFRP1+, WIF+/SFRP1−, WIF−/SFRP1+, and WIF−/SFRP1−) only coexpression of WIF1 and SFRP1 (WIF+/SFRP1+) was associated with favorable overall survival, together with low TNM stage, as an independent prognostic factor as shown in a multivariate survival model. The results indicated that WIF1 seemed to play an oncogenic role, while SFRP1 seemed to play an oncosuppressive role although both of them are secreted Wnt antagonists. Coexpression of SFRP1 and WIF1, rather than SFRP1 or WIF1 alone, could be used, together with low TNM stage, as a prognostic predictor of favorable outcomes in CRC.

scholarly journals Use of Serum FSH to Identify Perimenopausal Women with Pituitary hCG

2008 ◽  
Vol 54 (4) ◽  
pp. 652-656 ◽  
Author(s):  
Ann M Gronowski ◽  
Corinne R Fantz ◽  
Curtis A Parvin ◽  
Lori J Sokoll ◽  
Carmen L Wiley ◽  
...  
Keyword(s):  
Chart Review ◽  
Follicle Stimulating Hormone ◽  
Gestational Trophoblastic Disease ◽  
Diagnostic Utility ◽  
Medical Procedures ◽  
Older Patient ◽  
Patient Chart ◽  
Trophoblastic Disease ◽  
Perimenopausal Women ◽  
Rule Out

Abstract Background: Human chorionic gonadotropin (hCG) tests are performed on many female patients before performing medical procedures or administering medications that may harm a fetus. hCG of pituitary origin has been shown to increase with age. Therefore, mild increases in serum hCG in an older patient can be of pituitary origin and does not necessarily indicate pregnancy. The inability to rule out pregnancy in perimenopausal women can create clinical confusion and may delay needed therapies. Our objective was to determine the diagnostic utility of serum follicle-stimulating hormone (FSH) concentrations to rule out hCG of placental origin in perimenopausal women with a low concentration of serum hCG (5.0–14.0 IU/L). Methods: Seven testing centers performed 39 742 physician-ordered serum quantitative hCG tests over a 15-month period. From these, 100 samples from women 41–55 years of age with serum hCG concentrations 5–14 IU/L were identified. We performed FSH testing and patient chart review for each sample. Results: Twenty-three patients were found to have hCG of placental origin (pregnancy, resolving abortion, or gestational trophoblastic disease), and in those cases serum FSH was 0.4–43.8 IU/L. An FSH cutoff of 45.0 IU/L identified hCG of placental origin with 100% sensitivity and 75% specificity. FSH >45 IU/L was never observed when hCG was of placental origin (negative predictive value). Conclusions: These data indicate that quantitative serum FSH can be used to rule out pregnancy and hCG of placental origin in women 41–55 years of age with mild increase in serum hCG concentrations.

Spectrum of Pathological Lesions in Uterine Specimens with Focus on Gestational Trophoblastic Disease in Karachi

2020 ◽  
Keyword(s):  
Hydatidiform Mole ◽  
Endometrial Stromal Sarcoma ◽  
Gestational Trophoblastic Disease ◽  
Cross Sectional Study ◽  
Reproductive Age ◽  
P Value ◽  
Cross Sectional ◽  
Endometrial Polyps ◽  
Trophoblastic Disease ◽  
Proliferative Endometrium

Background: The most common benign pathological lesion in women of reproductive age is uterine leiomyoma. Gestational trophoblastic disease includes tumors and tumor like lesions originating from trophoblastic tissue. The aim of this study was to find the spectrum of molar pregnancy and uterine pathologies focusing on gestational trophoblastic disease as no study has been done in the past few years. Methods: Endometrial and uterine specimens of patients (n=436) between the ages of 15-65 years were collected from a private hospital in Karachi from December 2018 to December 2019. This cross-sectional study was carried out by pathological diagnosis of patients’ samples under light microscopy using hematoxylin and eosin staining. Stratification was done about age and nature of specimen to control the effect modifiers. The post stratification Chi square test was applied and p value <0.05 was considered significant. Results: Mean age of the patients was 36.1 years ±7.8. Total 436 uterine biopsies included 260(59.6%) hysterectomies, 56(12.8%) endometrial curetting’s, 117(26.8%) evacuation specimens and 3(0.7%) polypectomies. Common pathologies included 124(28.4%) leiomyomas, 61(14%) proliferative endometrium, 52(11.9%) adenomyosis and 32(7.3%) endometrial polyps. Gestational trophoblastic disease was seen in 9(2.06%). Seven (87.5%) were partial hydatidiform moles, one (12.5%) exaggerated placental site reaction and one choriocarcinoma. Mole was common between 26-30 years with mean age of 27.2 years and prevalence was 6/100 abortions. Conclusion: Leiomyoma was the commonest (28.4%) uterine pathology followed by proliferative endometrium (14.5%). However, endometrial stromal sarcoma and endometriosis were found 0.2% each. High prevalence of mole was seen in this study. Partial mole was most common and choriocarcinoma was least common. Keywords: Hydatidiform Mole; Pathology; Prevalence.

scholarly journals Choriocarcinoma with uterine rupture presenting as acute haemoperitoneum and shock

2017 ◽  
Vol 6 (3) ◽  
pp. 1141 ◽  
Author(s):  
Mamour Gueye ◽  
Mame Diarra Ndiaye Gueye ◽  
Ousmane Thiam ◽  
Youssou Toure ◽  
Mor Cisse ◽  
...  
Keyword(s):  
Young Woman ◽  
Uterine Rupture ◽  
Gestational Trophoblastic Disease ◽  
Uterine Perforation ◽  
Molar Pregnancy ◽  
Rare Neoplasm ◽  
Trophoblastic Disease ◽  
Intraperitoneal Bleeding ◽  
Invasive Mole

Choriocarcinoma is a rare neoplasm and a malignant form of gestational trophoblastic disease. Invasive mole may perforate uterus through the myometrium resulting in uterine perforation and intraperitoneal bleeding. But uterine perforation due to choriocarcinoma is rare. We present a case of a young woman who presented 1 year after uterine evacuation of a molar pregnancy with invasive choriocarcinoma complicated by a uterine rupture and haemoperitoneum.

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