Β-subunit Of Human Chorionic Gonadotropin Research Articles

Detection of the GH analog somatrogon in sports drug testing: Immunological approaches and LC-HRMS/MS.

Due to the presumed lipolytic and anabolic properties, the misuse of human growth hormone (hGH) and its synthetic analogs in sports is prohibited both in- and out-of-competition. Within this research project, the detectability of somatrogon, a recombinant fusion glycoprotein of 22 kDa hGH and the C-terminal peptide (CTP) of the human chorionic gonadotropin (hCG) β-subunit, with current WADA-approved doping control assays for hGH and hCG was investigated. For that purpose, cross-reactivity tests and a somatrogon administration study were conducted, and only "Kit 2" of the GH isoform differential immunoassays proved applicable to the detection of somatrogon administration in serum. In urine, the immunoassay specific for total hCG yielded presumptively positive findings for several post-administration samples, which can probably be attributed to the presence of an immunoreactive fragment of the hCG β-subunit. As the detectability of somatrogon with these approaches was found to be limited, a highly specific detection assay (LOD: 10ng/mL) for the drug in serum samples was developed by using affinity purification with GH receptor (GHR)-conjugated magnetic beads, proteolytic digestion, and liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). Following optimization, the approach was comprehensively characterized, and authentic post-administration serum samples were successfully analyzed as proof-of-concept, indicating a detection window of at least 96 h. Consequently, the presented method can be employed to confirm the presence of somatrogon in serum samples, where only "Kit 2" of the currently used immunoassay kits yielded an abnormally high Rec/Pit ratio.

Non-surgical management of patients with ectopic pregnancy: A review

An ectopic pregnancy is a medical emergency. Currently, surgery is the main method of therapy, and non-surgical management with methotrexate is considered an acceptable alternative. Methotrexate is a folic acid antagonist and has an inhibitory effect on the proliferation of trophoblast cells. There are various methotrexate regimens; the choice is based on the level of β-subunit of human chorionic gonadotropin, the location of the ectopic pregnancy and the patient's adherence to treatment. Therapy of ectopic tubal pregnancy with methotrexate is an effective and safe alternative to surgical treatment, does not affect the ovarian reserve and preserves the woman's fertility.

Total human chorionic gonadotropin is a more suitable diagnostic marker of gestational trophoblastic diseases than the free β-subunit of human chorionic gonadotropin

ObjectivesHuman chorionic gonadotropin (hCG) levels are essential for the management of trophoblastic diseases. This study aimed to compare the sensitivities and relationships of two hCG measurement methods (total hCG and the free β-subunit of hCG) in managing gestational trophoblastic disease (GTD). Design and MethodsWe analyzed data from patients treated for GTD at Chiba University Hospital between 2008 and 2019. We focused on cases where both total hCG (mIU/mL) and the free β-subunit of hCG (ng/mL) were measured on the same day. ResultsOut of 80 patients (mean age 38.9 ± 11.7 years) and 158 measurements, 26 had values below the sensitivity threshold for both tests. Fifty-nine measurements were positive for total hCG but below the sensitivity threshold for the free β-subunit of hCG, whereas only two showed the opposite. Seventy-one measurements were positive for both total hCG and the free β-subunit of hCG. There was a significant correlation between total hCG and the free β-subunit of hCG with both positive values, (r = 0.94, p < 0.001; Spearman's correlation test). Of the 85 measurements with undetectable free β-subunit levels, 26 also had undetectable total hCG levels. However, total hCG was detectable in 59 patients from these cases, with a median value (interquartile range) of 2.9 (1.75–4.9) mIU/mL. ConclusionsIn the management of GTD, the use of the free β-subunit system alone cannot be recommended.

A Two-Step Hysteroscopic Management for Cesarean Scar Pregnancy: A Proposal Method

Background: Cesarean Scar Pregnancy (CSP) is a cause of severe maternal morbidity. Currently, no guideline for its management is shared. We assessed safety and effectiveness of Methotrexate (MTX) administration within the sub-chorionic space under hysteroscopic guidance, followed by resectoscopic placental removal. Methods: Five patients suffering from type 2 CSP underwent a sequential treatment based on hysteroscopic techniques. Pregnancy termination was firstly obtained by injection of 80 mg of MTX within the intervillous spaces of placental site. The intervention was performed in an office setting using a 16Fr hysteroscope. MTX was administered by a 17-gauge needle suitable for the operative channel of hysteroscope. Subsequently, based on the decline of Human Chorionic Gonadotropin β-subunit (β-HCG), we timed a placental removal using a 27-Fr resectoscope, under conscious sedation. Results: In all women a diagnosis of CSP was achieved between 6 and 8 gestational age weeks. Hysteroscopic MTX administration resulted easily, quickly, painlessly and uneventfully in all patients. A substantial decrease of β-HCG was obtained in all patients within 15 days from the MTX administration. After a mean time of 27 days from MTX a resectoscopic removal of CSP was carried-out without any recorded adverse outcome. After 30 days from surgery β-HCG returned to non-pregnant level and normal physical findings were found in all patients. Conclusions: Hysteroscopy-guided MTX sub-chorionic administration resulted safe and effective for CSP termination. It was followed by successful and uneventful resectoscopic placenta removal in all patients. When hysteroscopy facilities are available, this combined therapy can be an option to treat CSP.

Ultrasound findings in prenatal diagnosis of trisomy 18 associated with elevated levels of maternal serum alpha-fetoprotein

Rationale: Trisomy 18, also referred to as Edwards syndrome, is the second most common autosomal trisomy syndrome. Trisomy 18 can be identified during prenatal screening by the detection of abnormal maternal serum results and one or more structural abnormalities on ultrasound. Previous studies confirmed that levels of pregnancy-related plasma protein A, alpha-fetoprotein, and free β-subunit of human chorionic gonadotropin in the serum of pregnant women carrying fetuses with trisomy 18 were lower than those in women with normal pregnancies. Patient concerns: A 29-year-old pregnant woman with a high risk of trisomy 18 underwent maternal serum screening at 16 weeks of gestation. The patient exhibited an elevated level of maternal serum alpha-fetoprotein (125 U/mL; 3.5225-fold higher than the multiple of the median). Ultrasonography revealed multiple abnormalities. Diagnoses: Culture of amniotic fluid cells revealed a karyotype of 47, XY, +18. Interventions and outcomes: The pregnancy was terminated. Lessons: Trisomy 18 can be identified prenatally by detection of abnormal levels of key proteins in the maternal serum, and detection of one or more structural abnormalities by ultrasound screening. Prenatal serological screening combined with ultrasound can effectively diagnose fetuses with trisomy 18 in the second trimester.

The Role of Human Chorionic Gonadotropin Beta (hCGβ) in HPV-Positive and HPV-Negative Oropharyngeal Squamous Cell Carcinoma.

Simple SummaryOropharyngeal squamous cell carcinoma (OPSCC) is often associated with human papillomavirus (HPV). The management of OPSCC remains a challenge, and HPV-negative disease is commonly associated with impaired survival. Novel insights into diagnostics and treatment modalities are warranted to improve disease outcome. Various potential biomarkers affecting prognosis in OPSCC have been distinguished. Our aim was to study the role of the free β-subunit of human chorionic gonadotropin hormone in HPV-negative and HPV-positive OPSCC.Background: This study was carried out to observe the upregulation of the free β-subunit of human chorionic gonadotropin (hCGβ) and its prognostic significance in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC). Materials and methods: A total of 90 patients with OPSCC treated with curative intent at the Helsinki University Hospital (HUS), Helsinki, Finland, during 2012–2016 were included. Serum samples were collected prospectively, and their hCGβ concentrations (S-hCGβ) were determined by an immunofluorometric assay. The expression of hCGβ in tumor tissues was defined by immunohistochemistry (IHC). HPV determination was performed by combining p16-INK4 IHC and HPV DNA PCR genotyping. Overall survival (OS) and disease-specific survival (DSS) were used as survival endpoints. Results: S-hCGβ positivity correlated with poor OS in the whole patient cohort (p < 0.001) and in patients with HPV-negative OPSCC (p < 0.001). A significant correlation was seen between S-hCGβ and poor DSS in the whole cohort (p < 0.001) and in patients with HPV-negative OPSCC (p = 0.007). In a multivariable analysis, S-hCGβ was associated with poor DSS. Of the clinical characteristics, higher cancer stage and grade were associated with S-hCGβ positivity. No statistically significant correlation with tissue positivity of hCGβ was seen in these analyses. Conclusion: S-hCGβ may be a potential independent factor indicating poor prognosis, notably in HPV-negative OPSCC.

Диагностика преэклампсии на основании показателей скрининга I триместра и компонентов состава тела

BACKGROUND: According to a large amount of clinical and experimental material, of international protocols of treatment and management of patients, of screening tests, the prevalence of preeclampsia shows no tendency to decline. Absence of possibilities to act on the processes leading to PE, as well as ineffective measures of prevention of this pathology, determine the need for implementation of research for early identification of groups of risk and prevention of PE. AIM: To identify possible markers of development of preeclampsia based on the parameters of the first trimester screening and body composition components in pregnant women without obesity up to 15 weeks of gestation. MATERIALS AND METHODS: A study of 747 women without obesity of 11 to 13 weeks and 6 days of gestation including 30 women with different variants of arterial hypertension and 669 women with physiological pregnancy, was conducted on the base of the Regional Perinatal Center of Yaroslavl. All the women underwent Doppler velocimetry of the uterine arteries, assessment of β-subunit of human chorionic gonadotropin (β-HCG) and pregnancy–associated plasma protein A (PAPP-A) in the blood, examination of the components of body composition and analysis of the maternity case record with history of childbirth. RESULTS: Increase in the pulsation index was identified in Doppler velocimetry of the uterine arteries with sensitivity of 64.7% and specificity of 68.2% in the group with the subsequent development of preeclampsia. PAPP-A was found to have the maximum sensitivity of 45.7% and specificity of 75.5% in identification of the risk group for preeclampsia by blood parameters. No differences in the body composition were found in the study groups. No significant increase in the prognostic capacity of simultaneous analysis of the data of Doppler velocimetry and biochemical examinations and of components of the body composition was found. CONCLUSION: Doppler velocimetry of the uterine arteries is an effective non-invasive screening method for identification of the risk group for development of preeclampsia in pregnant women without obesity.

Predicting Hypertensive Disease in the First Trimester of Pregnancy: Risk Models and Analysis of Serum D-dimer Levels Combined with Plasma Pregnancy-Associated Protein A, Free β-Subunit of Human Chorionic Gonadotropin, and Fetal Nuchal Translucency.

We aimed to investigate the predictive ability of serum levels of D-dimer (DD) in the first trimester for the occurrence of hypertensive disorders of pregnancy (HDP). In this retrospective, case-cohort study, we measured the levels of DD, plasma pregnancy-associated protein A (PAPP-A), and free β-subunit of human chorionic gonadotropin (free β-hCG) and analyzed fetal nuchal translucency (NT) in 150 healthy gravidas, 126 cases of gestational hypertension (GH), 53 cases of preeclampsia (PE), and 41 cases with severe preeclampsia (SPE). Likelihood ratio models and risk models were built using single markers (DD, PAPP-A, free β-hCG, and NT) and combinations of those markers. Analyses showed that the levels of DD multiple of the median (MoM) in the GH, PE, and SPE groups were all significantly higher than those in the control group, with significant differences between groups (χ2 = 70.325, P < 0.001). The area under curve (AUCs) for DD in the GH, PE, and SPE groups was 0.699, 0.784, and 0.893, respectively; the positive likelihood ratio (+LR) was 1.534, 1.804, and 2.941, respectively; and the negative likelihood ratio (-LR) was 0.022, 0.081, and 0, respectively. When the cut-off values of DD for the GH, PE, and SPE groups were 0.725, 0.815, and 0.945 MoM, respectively, the corresponding sensitivities were 0.992, 0.962, and 1.000, respectively. As gestational hypertension progressed, the levels of DD tended to increase gradually. The maternal serum level of DD in the first trimester had correlative and diagnostic value for HDP. The sensitivity and specificity of maternal serum levels of DD level in the first trimester for different types of HDP were significantly different; the best sensitivity and specificity were detected in the SPE group. First trimester DD level, combined with other biochemical markers, may improve our ability to diagnose HDP.

An Assessment of Selected Molecular and Biochemical Markers of the Folate Pathway as Potential Risk Factors for Fetal Trisomy 21 during the First Trimester of Pregnancy in the Polish Population.

Are the maternal gene variants MTHFR: c.665C>T, MTHFR: c.1286A>C, MTR: c.2756A>G, MTRR: c.66A>G, RFC1: c.80C>T and TCN2: c.776G>C and blood markers of the folate pathway important factors in assessing the risk of fetal trisomy 21 (fetal-T21)? Twenty pregnant women with a high risk and twenty with a low risk of fetal-T21 underwent prenatal examination. Selected gene variants and folate pathway markers and pregnancy-associated plasma protein A (PAPP-A) and free β-subunit of human chorionic gonadotropin β (free-β-hCG) multiple of the medians (MoMs) were determined. The distributions of the alternative alleles and genotypes of the gene variants did not differ between the studied groups. There was no relationship between PAPP-A and β-hCG MoM values and the presence of allele alternative genotype variants. The occurrence of alternative variants of the selected genes and concentrations of most of the studied folate pathway markers may not play a crucial role in the risk of fetal-T21 in pregnant women. However, the relationships between erythrocyte folate concentrations and the occurrence of alternative variants: c.665C>T MTHFR and c.776G>C TCN2, as well as the methylmalonic acid concentration and the occurrence of alternative variant c.776G>C TCN2 in pregnant women with fetal-T21, encourage further research. So far, of the biochemical markers, maternal PAPP-A and β-hCG MoM values remain independent risk factors for fetal-T21.

Biliary hCGβ Is a Potential Novel Marker for Prediction of Biliary Neoplasia in Primary Sclerosing Cholangitis Patients

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease, which is associated with an increased risk of cholangiocarcinoma (CCA). Novel markers, to complement or replace CA19-9, are urgently needed for the screening of PSC-associated biliary neoplasia. Previous studies have suggested that serum trypsinogen-2 and human chorionic gonadotropin β-subunit (hCGβ) may serve as such markers. Using highly specific in-house immunoassays, we studied trypsin(ogen)-2 and -3, SPINK1 and hCGβ in bile samples of 214 patients, referred for endoscopic retrograde cholangiography. We found that biliary trypsinogen-2 was decreased (p = 0.027) and hCGβ was elevated (p &lt; 0.001) in PSC patients who were diagnosed 1.6 years (median, range 0.1–8.8 years) later with CCA or in whom biliary dysplasia was observed at least twice in brush cytology (n = 11) as compared to PSC patients without CCA or repeated dysplasia (n = 171). The other studied markers did not show significant differences between these groups. Our results warrant further evaluation of hCGβ as a predictive marker for PSC-associated biliary neoplasia.

Primary mediastinal germ cell tumours: an immunohistochemical and molecular diagnostic approach.

Primary mediastinal germ cell tumours (PMGCTs) are rare mediastinal neoplasms, and their diagnosis can be challenging, owing to small biopsy samples. The aim of this study was to develop a diagnostic algorithm using immunohistochemical staining, with a focus on novel markers, and molecular analysis of isochromosome 12p [i(12p)]. Paraffin-embedded tissues of 32 mediastinal tumours were analysed with immunohistochemical staining for sal-like transcription factor 4 (SALL4), Lin-28 homologue A (LIN28), octamer-binding transcription factor 3/4 (OCT3/4), D2-40, cluster of differentiation 117 (CD117), sex-determining region Y-box 17, sex-determining region Y-box 2 (SOX2), cluster of differentiation 30, the β-subunit of human chorionic gonadotropin (β-hCG), GATA-binding protein 3 (GATA3), forkhead box protein A2 (FOXA2), glypican-3 (GPC3), α-fetoprotein (AFP), terminal deoxynucleotidyl transferase (TdT), nuclear protein of the testis (NUT), and pan-cytokeratin. Quantitative real-time polymerase chain reaction was performed to investigate the i(12p) status. Fifteen seminomas, seven teratomas, one yolk sac tumour, one choriocarcinoma and seven mixed PMGCTs were diagnosed. Each entity had different immunohistochemical staining patterns, which helped to distinguish them: OCT3/4, D2-40, CD117 and TdT for seminoma; OCT3/4 and SOX2 for embryonal carcinoma; FOXA2, GPC3 and AFP for yolk sac tumour; and β-hCG and GATA3 for choriocarcinoma. Mature teratomas stained positively for pan-cytokeratin in epithelial components and focally for SALL4, SOX2, GATA3, D2-40, and FOXA2. Furthermore, a NUT carcinoma mimicking a PMGCT was diagnosed, showing strong nuclear SOX2 staining and speckled nuclear NUT staining. i(12p) was detected in 24 of 27 PMGCTs (89%). A diagnostic algorithm is of great importance for a reliable diagnosis of PMGCT in, usually small, tissue biopsy samples. Therefore, a combination of three to four antibodies to identify the correct histological subtype is usually necessary, in addition to morphological features. The i(12p) status serves as an additional option to indicate a germ cell origin in selected cases.

Second trimester maternal serum D-dimer combined with alpha-fetoprotein and free \u03b2-subunit of human chorionic gonadotropin predict hypertensive disorders of pregnancy: a systematic review and retrospective case\u2013control study

BackgroundThis study investigated whether maternal serum D-dimer (DD) alone or DD combined with alpha-fetoprotein (AFP) and free β-subunit of human chorionic gonadotropin (free β-hCG) in the second trimester could be used to predict hypertensive disorders of pregnancy (HDP).Materials and methodsIn this retrospective case–control study, the data of gravidas patients who delivered at hospital were divided into the following groups: control (n = 136), gestational hypertension (GH, n = 126), preeclampsia (PE, n = 53), and severe preeclampsia (SPE, n = 41). Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic value of maternal serum DD, AFP, and free β-hCG levels for HDP.ResultsDD levels of the GH, PE, and SPE groups were significantly higher than that of the control group (P < 0.001). The order of effectiveness for models predicting HDP was as follows: DD + AFP + free β-hCG > DD > DD + AFP > DD + free β-hCG > AFP + free β-hCG > AFP > free β-hCG. For predicting different types of HDP, DD alone had the best diagnostic value for SPE, followed by PE and GH. DD alone had a sensitivity of 100% with a 0% false negative rate and had the highest positive likelihood ratio (+ LR) for SPE. DD alone in combination with AFP alone, free β-hCG alone and AFP + free β-hCG could reduce false positive rate and improve + LR.ConclusionDD is possible the best individual predictive marker for predicting HDP. Levels of DD alone in the second trimester were positively correlated with the progression of elevated blood pressure in the third trimester, demonstrating the predicting the occurrence of HDP. The risk calculation model constructed with DD + free β-hCG + AFP had the greatest diagnostic value for SPE.

Detection of Circulating Tumor Cells (CTCs) in Patients with Testicular Germ Cell Tumors.

While the majority of patients with advanced testicular germ cell tumors (GCT) achieve complete responses after chemotherapy and if indicated after postchemotherapy resection of residual lesions, about 20% of patients have incomplete responses or show relapses. Moreover, toxicity of chemotherapy is high, and severe adverse chronic effects have been described. Therefore, there is an urgent need for biomarkers that could help to improve tumor staging, and support decision-making, ideally including monitoring of therapy response and prediction of relapse. Besides the well-established serum markers lactate dehydrogenase, α-fetoprotein, and β-subunit of human chorionic gonadotropin, during recent years new noninvasive liquid biopsy markers have been investigated in GCT, including cell-free nucleic acids like microRNAs, and circulating tumor cells (CTCs).Prognostic relevance has been demonstrated for circulating tumor cells (CTCs) in patients with different cancers. However, little is known in GCT patients. Histologically, GCT are a very heterogeneous group of tumors comprising pure seminomas (consisting of cells that remember primordial germ cells) and nonseminomas, which are either undifferentiated (embryonal carcinoma) or differentiated, exhibiting different degrees of embryonic (teratoma) or extraembryonic (yolk sac tumor and choriocarcinoma) differentiation. This heterogeneity hampers capture and detection of CTCs deriving from those tumors using a single method or a single antibody. To date, label-independent capture methods that enrich tumor cells according to the density of GCT cells, which is similar to that of mononuclear cells, have been successfully applied. Since testicular GCT might also express epithelial proteins, methods based on enrichment of CTCs using epithelial markers are promising to detect CTCs in certain subgroups of patients with GCTs as well.Here, we describe and discuss a combination of methods to capture and detect GCT cells with epithelial and germ cell characteristics in blood.

Health technology assessment in obstetrics: advantage of tailored conservative strategy vs surgical therapies of monochorionic twin complicated by TRAP-sequence

Introduction.Twin reversed arterial perfusion (TRAP) syndrome is one of the types of complications of monochorial twins (MT) with a frequency of occurrence of 1:35000 births. It is characterized by the presence of the main vessel instead of a normal 4 chambers heart and intrauterine developmental abnormalities. This pregnancy requires monitoring using dynamic ultrasound diagnostics every 7 days, in accordance with current recommendations. The treatment is intrauterine laser coagulation of blood vessels of the “acardial fetus” (AP) in order to prevent the development of a threatening condition for the “fetal pump” (PP). Aim: to demonstrate the possibilities of comprehensive conservative management of monochorial pregnancy complicated by TRAP.Materials and methods. An ultrasound examinations were performed on a weekly basis in monochorionic pregnancy, complicated by TRAP within the period 12-38 weeks. Serum concentrations of biochemical markers PAPP-A (pregnancy-associated plasma protein-A) and β-hGC (β-subunit of human chorionic gonadotropin) were studied in the first trimester to predict adverse perinatal outcomes.Results. The possibility of prolonging a pregnancy complicated by TRAP without performing intrauterine surgical intervention, during which quite serious complications can occur in this category of pregnancies, has been demonstrated. In a patient with monochorionic twins complicated by TRAP, totally 27 ultrasound examinations were performed within the period 12-38 weeks. This approach made it possible to dynamically monitor the condition of a pregnant and healthy fetus and to prolong pregnancy without surgery until the full term.Conclusions.Following the existing guidelines, without tailoring for individual risk, may lead to an unreasonable increase in surgical interventions. In turn, surgery is not only accompanied by a high risk of complications (up to 15%), but also constitute a certain financial burden on the budget, determined by the state on the level of 208,000 rubles. Performing routine ultrasound examinations according to the examination protocol for monochorionic pregnancy will contribute to avoiding the complications associated with surgery and better selection for surgery as well as reducing the government costs.

Correlation and diagnostic value of maternal serum alpha-fetoprotein level, predelivery age and body mass with gestational diabetes mellitus

To investigate the correlation and diagnostic value of maternal serum alpha-fetoprotein (MSAFP) level, predelivery age and body mass with gestational diabetes mellitus (GDM) at 9 ∼ 13 + 6 weeks (early pregnancy) and 15 ∼ 20 + 6 weeks (middle pregnancy). 486 normal and 1290 GDM women were examined for serum pregnancy-associated plasma protein A (PAPP-A), MSAFP, free β-subunit of human chorionic gonadotropin (free β-hCG) and nuchal transparency (NT) levels. Binary logistic regression analysis was used to analyze the risk factors and calculate the Odds ratio (OR) of each relevant variable. In GDM group, the predelivery age, body mass in early pregnancy and middle pregnancy were statistically higher than that in control group. The level of MSAFP in GDM group was 0.97(0.54–1.86) MOM, higher than that in control group 0.92 (0.51–1.78), (z = 3.159, p = .002). Area under curve (AUC) of MSAFP, age and body mass to GDM was 0.549, 0.645 and 0.625, respectively. The level of MSAFP, predelivery age and body mass are associated with GDM, which may be helpful for the prediction of GDM in late pregnant women. However, PAPP-A, NT and free β-hCG during pregnancy have no predicting value for GDM.

Successful Management of Cervical Ectopic Pregnancy: A Case Report

Background: Cervical ectopic pregnancy is a rare condition with an incidence of less than 0.1% in all ectopic pregnancies. This life-threatening condition is associated with a high morbidity and mortality rates. Recently, the recommended protocol for the treatment of cervical ectopic pregnancy is fertility preservation rather than invasive surgery and hysterectomy. The aim of this report was to introduce a case of successful management of cervical ectopic pregnancy. Case report: A 31-year-old woman was presented with her third pregnancy with a history of one cesarean section and spontaneous abortion. She was admitted to an academic hospital with vaginal bleeding following 10 weeks of amenorrhea. Based on transvaginal ultrasound, a live fetus of about nine weeks was reported, located in the cervical canal. The β-subunit of human chorionic gonadotropin (βhCG) titer was reported as 108000 mIU/m. Cervical pregnancy diagnosis was consistent. In order to preserve fertility based on the patient’s hemodynamic status, medical treatment and surgical intervention, including methotrexate and then intravaginal ligation of cervical branches of uterine arteries, and subsequently cervical tampon was successfully performed. Conclusion: The early detection and accurate diagnosis of cervical ectopic pregnancy using ultrasound and serial βhCG titer can be a valuable approach. Appropriate and conservative management has decreased the morbidity rate and preserved the ongoing fertility in the affected patients.

Evaluation of Circulating miRNA Biomarkers of Testicular Germ Cell Tumors during Therapy and Follow-up-A Copenhagen Experience.

New microRNA-based serum biomarkers (miRNA-367-3p, -371a-3p, -372-3p, and -373-3p) have shown great potential for the detection of testicular germ cell tumors (TGCTs), but few studies have investigated the clinical utility and performance of these tests in treatment monitoring. In this study, circulating miRNA levels were measured, together with serum tumor markers alpha-fetoprotein (AFP), β-subunit of human chorionic gonadotropin (β-HCG) and lactate dehydrogenase (LDH) in 406 consecutive blood samples obtained during the treatment and follow-up of 52 TGCT patients at the Copenhagen University Hospital. After testing three different methods of RNA isolation from peripheral blood and PCR quantification in a subset of samples (n = 15), the best performing setup of targeted isolation of miRNAs inside and outside exosomes was selected to analyze all samples. At primary diagnosis, the miRNAs significantly outperformed the serum tumor markers, with a sensitivity and specificity of 78% and 100% (based on 40 patients), respectively. The picture was not as clear when patient trajectories were investigated, with both positive and negative signals for miRNAs and serum tumor markers. To establish whether measuring miRNAs adds value beyond the primary diagnosis, large prospective clinical trials comparing miRNAs and classical tumor markers during the treatment and follow-up of TGCT patients are needed.

Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer.

Testicular cancer is an important disease with increasing incidence and a high burden of morbidity and mortality in young men worldwide. Histological examination of the testicular tissue after orchiectomy plays an important role alongside patient history, imaging, clinical presentation and laboratory parameters. Surgical procedures and chemotherapeutic treatment provide a high chance of cure in early stages, though some patients in advanced stages belonging to a poor risk group experience cancer-related death. Though conventional serum-based tumor markers, including α-fetoprotein (AFP), the β-subunit of human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH), are useful as prognostic and diagnostic biomarkers, unfortunately, these tumor markers only have a sensitivity of about 60%, and in pure seminoma even lower with about 20%. Therefore, the development of new tumor markers is an important and intensively ongoing issue. The analysis of epigenetic modification and non-coding RNA microRNAs (miRNAs) are carrying most promising potential as tumor markers in future. miRNAs are small RNAs secreted by testicular tumor cells and circulate and be measurable in body fluids. In recent years, miRNAs of the miR-371-373 cluster in particular have been identified as potentially superior tumor markers in testicular cancer patients. Studies showed that miR-371a-3p and miR-302/367 expression significantly differ between testicular tumors and healthy testicular tissue. Several studies including high prospective multi-center trials clearly demonstrated that these miRNAs significantly exceed the sensitivity and specificity of conventional tumor markers and may help to facilitate the diagnosis, follow-up, and early detection of recurrences in testicular cancer patients. In addition, other miRNAs such as miR-223-3p, miR-449, miR-383, miR-514a-3p, miR-199a-3p, and miR-214 will be discussed in this review. However, further studies are needed to identify the value of these novel markers in additional clinical scenarios, including the monitoring in active surveillance or after adjuvant chemotherapy, but also to show the limitations of these tumor markers. The aim of this review is to give an overview on the current knowledge regarding the relevance of non-coding miRNAs as biomarkers in testicular cancer.

Activin-inhibitory action on lactotrophs is decreased in lactotroph hyperplasia.

Among all the hormone-secreting pituitary tumours, prolactinomas are the most frequently found in the clinic. Since dopamine is the primary inhibitor of lactotroph function, dopamine agonists represent the first-line therapy. However, a subset of patients exhibits resistance to these drugs, and therefore, alternative treatments are desired. As activins inhibit prolactin gene expression through the inhibition of Pit-1 involving the p38MAPK pathway, in the present work, we studied the local activin system as an alternative inhibitory system for lactotroph hyperplasia treatment. We used two different mouse models of prolactinoma: transgenic mice with overexpression of the human chorionic gonadotropin β-subunit (hCGβ) and mice lacking dopamine receptor type 2. In both models, females, but not males, develop lactotroph hyperplasia from the fourth month of life. We found reduced expression of pituitary activin subunits and activin receptors in hyperplastic pituitaries from both models compared with wild-type counterparts. Consequently, hyperplastic pituitaries presented a reduced activin-inhibitory action on prolactin secretion. Additionally, while female wild-type lactotrophs presented high levels of phospho-p38MAPK, it was lost in prolactinomas, concomitant with decreased activin expression, increased Pit-1 expression and tumour development. In contrast, male pituitaries express higher mRNA levels of activin subunits βA and βB, which would suggest a stronger activin inhibitory function on lactotrophs, protecting this sex from tumour development, despite genotype. The present results highlight the importance of the activin inhibitory action on lactotroph function and place the local activin system as a new target for the treatment of dopamine agonist-resistant prolactinomas.

Effect of Chlorpyrifos on human extravillous-like trophoblast cells

An increased risk of pregnancy disorders has been reported in women and animal models exposed to organophosphate pesticides. However, less information is available on impacts to human placental function. Here, we addressed the impact of chlorpyrifos (CPF) on extravillous cytotrophoblasts (evCTB) employing HTR8/SVneo cells as an in vitro model. Cell proliferation, migration and invasion were not affected by CPF under conditions where cell viability was not compromised; however, we observed reduced expression of genes for vascular endothelial growth factor receptor 1, hypoxia-inducible factor 1-alpha, peroxisome proliferator activated receptor gamma, and the β-subunit of human chorionic gonadotropin. These results are the first effects reported by organophosphate pesticide in evCTB cells and show altered expression of several genes important for placental development that could serve as potential biomarkers for future research.