scholarly journals HE4 in Various Body Fluids: A Prospective Pilot Study

2020 ◽  
pp. 1-6
Author(s):  
Anna Stiekema ◽  
Anna Stiekema ◽  
CM Korse ◽  
TC Linders ◽  
JOAM van Baal ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Body Fluids ◽  
Cervical Mucus ◽  
Healthy Controls ◽  
Ovarian Mass ◽  
Creatinine Concentration ◽  
Human Epididymis Protein 4 ◽  
Non Invasive ◽  
Specific Serum ◽  
Malignant Ovarian Tumor

Introduction: Human epididymis protein 4 (HE4) is a glycoprotein that is a sensitive and specific serum biomarker for patients with suspected ovarian cancer. HE4 is also secreted in different body fluids such as cervical mucus or urine, which could provide an easy alternative for screening purposes. HE4 protein secretion in different body fluids was analysed in 11 healthy controls and in 10 patients with a benign, 10 with a borderline and 22 with a malignant ovarian tumor. Materials and Methods: Preoperative samples of serum, urine, cervical mucus, saliva, and ascites were collected to measure HE4 with an ELISA assay. Urinary creatinine concentration and cervical total protein concentrations were used as reference analytes, and ratios with HE4 were calculated. Results: Median HE4 concentration in urine was higher in patients with epithelial ovarian cancer (EOC) compared to healthy controls and patients with a benign or borderline mass (p=0.02). HE4/creatinine ratio could differentiate healthy controls from EOC and benign ovarian disease from EOC (AUC 0.76, 95% CI 0.58-0.94 and AUC 0.71, 95% 0.52-0.89, respectively). HE4 in ascites was significantly higher in patients with EOC or borderline ovarian mass compared to patients with a benign ovarian mass (p=0.04). HE4 concentrations in cervical mucus and saliva were not significantly higher in patients with EOC. Conclusion: This study shows that HE4 is abundant in body fluids other than blood and suggests that urinary HE4 levels can be used as a non-invasive diagnostic alternative to detect EOC.

Optimization of Extraction Parameters of Reverse Iontophoretic Determination of Blood Glucose in an Artificial Skin Model

2020 ◽  
Vol 16 (6) ◽  
pp. 722-737
Author(s):  
Cigdem Yengin ◽  
Emrah Kilinc ◽  
Fatma Gulay Der ◽  
Mehmet Can Sezgin ◽  
Ilayda Alcin
Keyword(s):  
Ionic Strength ◽  
Body Fluids ◽  
Extraction Time ◽  
Artificial Skin ◽  
Dialysis Membrane ◽  
Skin Model ◽  
Non Invasive ◽  
Electrode Distance ◽  
Experimental Parameters

Background: Reverse İontophoresis (RI) is one of the promising non-invasive technologies. It relies on the transition of low magnitude current through the skin and thus glucose measurement becomes possible as it is extracted from the surface during this porter current flow. Objective: This paper deals with the development and optimization of an RI determination method for glucose. CE dialysis membrane based artificial skin model was developed and the dependence of RI extraction on various experimental parameters was investigated. Method: Dependence of RI extraction performance on noble electrodes (platinum, silver, palladium, ruthenium, rhodium) was checked with CA, CV and DPV, in a wide pH and ionic strength range. Optimizations on inter-electrode distance, potential type and magnitude, extraction time, gel type, membrane MWCO, usage frequency, pretreatment, artificial body fluids were performed. Results: According to the optimized results, the inter-electrode distance was 7.0 mm and silver was the optimum noble metal. Optimum pH and ionic strength were achieved with 0.05M PBS at pH 7.4. Higher glucose yields were obtained with DPV, while CA and CV achieved almost the same levels. During CA, +0.5V achieved the highest glucose yield and higher potential even caused a decrease. Glucose levels could be monitored for 24 hours. CMC gel was the optimum collection media. Pretreated CE membrane with 12kD MWCO was the artificial skin model. Pretreatment affected the yields while its condition caused no significant difference. Except PBS solution (simulated as artificial plasma), among the various artificial simulated body fluids, intestinal juice formulation (AI) and urine formulation U2 were the optimum extraction media, respectively. Conclusion: In this study, various experimental parameters (pretereatment procedure, type and MWCO values of membranes, inter-electrode distance, electrode material, extraction medium solvents, ionic strength and pH, collection medium gel type, extraction potential type and magnitude, extraction time and etc) were optimized for the non-invasive RI determination of glucose in a CE dialysis membrane-based artificial skin model and various simulated artificial body fluids.

scholarly journals A MYC-Driven Plasma Polyamine Signature for Early Detection of Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 913
Author(s):  
Johannes Fahrmann ◽  
Ehsan Irajizad ◽  
Makoto Kobayashi ◽  
Jody Vykoukal ◽  
Jennifer Dennison ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Stage ◽  
Area Under The Curve ◽  
Polyamine Metabolism ◽  
Healthy Controls ◽  
Test Set ◽  
Exact Test ◽  
Oncogenic Driver ◽  
Characteristic Area ◽  
Validation Set

MYC is an oncogenic driver in the pathogenesis of ovarian cancer. We previously demonstrated that MYC regulates polyamine metabolism in triple-negative breast cancer (TNBC) and that a plasma polyamine signature is associated with TNBC development and progression. We hypothesized that a similar plasma polyamine signature may associate with ovarian cancer (OvCa) development. Using mass spectrometry, four polyamines were quantified in plasma from 116 OvCa cases and 143 controls (71 healthy controls + 72 subjects with benign pelvic masses) (Test Set). Findings were validated in an independent plasma set from 61 early-stage OvCa cases and 71 healthy controls (Validation Set). Complementarity of polyamines with CA125 was also evaluated. Receiver operating characteristic area under the curve (AUC) of individual polyamines for distinguishing cases from healthy controls ranged from 0.74–0.88. A polyamine signature consisting of diacetylspermine + N-(3-acetamidopropyl)pyrrolidin-2-one in combination with CA125 developed in the Test Set yielded improvement in sensitivity at >99% specificity relative to CA125 alone (73.7% vs 62.2%; McNemar exact test 2-sided P: 0.019) in the validation set and captured 30.4% of cases that were missed with CA125 alone. Our findings reveal a MYC-driven plasma polyamine signature associated with OvCa that complemented CA125 in detecting early-stage ovarian cancer.

scholarly journals Automated Assay of a Four-Protein Biomarker Panel for Improved Detection of Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 325
Author(s):  
Christopher Walker ◽  
Tuan-Minh Nguyen ◽  
Shlomit Jessel ◽  
Ayesha B. Alvero ◽  
Dan-Arin Silasi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Predictive Value ◽  
Early Stage ◽  
Ca 125 ◽  
Healthy Controls ◽  
Classification Models ◽  
Serum Samples ◽  
Protein Biomarker ◽  
Biomarker Panel

Background: Mortality from ovarian cancer remains high due to the lack of methods for early detection. The difficulty lies in the low prevalence of the disease necessitating a significantly high specificity and positive-predictive value (PPV) to avoid unneeded and invasive intervention. Currently, cancer antigen- 125 (CA-125) is the most commonly used biomarker for the early detection of ovarian cancer. In this study we determine the value of combining macrophage migration inhibitory factor (MIF), osteopontin (OPN), and prolactin (PROL) with CA-125 in the detection of ovarian cancer serum samples from healthy controls. Materials and Methods: A total of 432 serum samples were included in this study. 153 samples were from ovarian cancer patients and 279 samples were from age-matched healthy controls. The four proteins were quantified using a fully automated, multi-analyte immunoassay. The serum samples were divided into training and testing datasets and analyzed using four classification models to calculate accuracy, sensitivity, specificity, PPV, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Results: The four-protein biomarker panel yielded an average accuracy of 91% compared to 85% using CA-125 alone across four classification models (p = 3.224 × 10−9). Further, in our cohort, the four-protein biomarker panel demonstrated a higher sensitivity (median of 76%), specificity (median of 98%), PPV (median of 91.5%), and NPV (median of 92%), compared to CA-125 alone. The performance of the four-protein biomarker remained better than CA-125 alone even in experiments comparing early stage (Stage I and Stage II) ovarian cancer to healthy controls. Conclusions: Combining MIF, OPN, PROL, and CA-125 can better differentiate ovarian cancer from healthy controls compared to CA-125 alone.

scholarly journals An SPRi Biosensor for Determination of the Ovarian Cancer Marker HE4 in Human Plasma

Sensors ◽  
2021 ◽  
Vol 21 (10) ◽  
pp. 3567
Author(s):  
Beata Szymanska ◽  
Zenon Lukaszewski ◽  
Beata Zelazowska-Rutkowska ◽  
Kinga Hermanowicz-Szamatowicz ◽  
Ewa Gorodkiewicz
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Tumor Resection ◽  
Analytical Signal ◽  
Cancer Marker ◽  
Human Epididymis Protein 4 ◽  
Pearson Coefficient ◽  
Rabbit Polyclonal Antibody ◽  
Good Agreement

Human epididymis protein 4 (HE4) is an ovarian cancer marker. Various cut-off values of the marker in blood are recommended, depending on the method used for its determination. An alternative biosensor for HE4 determination in blood plasma has been developed. It consists of rabbit polyclonal antibody against HE4, covalently attached to a gold chip via cysteamine linker. The biosensor is used with the non-fluidic array SPRi technique. The linear range of the analytical signal response was found to be 2–120 pM, and the biosensor can be used for the determination of the HE4 marker in the plasma of both healthy subjects and ovarian cancer patients after suitable dilution with a PBS buffer. Precision (6–10%) and recovery (101.8–103.5%) were found to be acceptable, and the LOD was equal to 2 pM. The biosensor was validated by the parallel determination of a series of plasma samples from ovarian cancer patients using the Elecsys HE4 test and the developed biosensor, with a good agreement of the results (a Pearson coefficient of 0.989). An example of the diagnostic application of the developed biosensor is given—the influence of ovarian tumor resection on the level of HE4 in blood serum.

scholarly journals BARD1 Autoantibody Blood Test for Early Detection of Ovarian Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 969
Author(s):  
Maxim Pilyugin ◽  
Magda Ratasjka ◽  
Maciej Stukan ◽  
Nicole Concin ◽  
Robert Zeillinger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Blood Test ◽  
Menopausal Status ◽  
Clinical Samples ◽  
Average Risk ◽  
Healthy Controls ◽  
Cancer Antigen 125 ◽  
Cancer Syndrome ◽  
Ovarian Cancer Screening

Background: Ovarian cancer (OC) is the most lethal gynaecological cancer. It is often diagnosed at an advanced stage with poor chances for successful treatment. An accurate blood test for the early detection of OC could reduce the mortality of this disease. Methods: Autoantibody reactivity to 20 epitopes of BARD1 and concentration of cancer antigen 125 (CA125) were assessed in 480 serum samples of OC patients and healthy controls. Autoantibody reactivity and CA125 were also tested for 261 plasma samples of OC with or without mutations in BRCA1/2, BARD1, or other predisposing genes, and healthy controls. Lasso statistic regression was applied to measurements to develop an algorithm for discrimination between OC and controls. Findings and interpretation: Measurement of autoantibody binding to a number of BARD1 epitopes combined with CA125 could distinguish OC from healthy controls with high accuracy. This BARD1-CA125 test was more accurate than measurements of BARD1 autoantibody or CA125 alone for all OC stages and menopausal status. A BARD1-CA125-based test is expected to work equally well for average-risk women and high-risk women with hereditary breast and ovarian cancer syndrome (HBOC). Although these results are promising, further data on well-characterised clinical samples shall be used to confirm the potential of the BARD1-CA125 test for ovarian cancer screening.

scholarly journals Non‐invasive assessment of temporal changes in myocardial microvascular function in persons with type 2 diabetes and healthy controls

2021 ◽  
Author(s):  
Ida K. B. Rasmussen ◽  
Philip Hasbak ◽  
Bernt J. Scholten ◽  
Jens C. Laursen ◽  
Emilie H. Zobel ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Temporal Changes ◽  
Microvascular Function ◽  
Healthy Controls ◽  
Non Invasive

scholarly journals A MOLECULAR-BASED APPROACH TO INVESTIGATE BREAST CANCER 1 AND BREAST CANCER 2 STATUS IN OVARIAN CANCER AMONG IRAQI WOMEN

2018 ◽  
Vol 11 (7) ◽  
pp. 199
Author(s):  
Muhannad Shweash ◽  
Saddam Jumaa Naseer ◽  
Maisam Khider Al-anii ◽  
Thulfiqar Fawwaz Mutar
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Patients ◽  
Gene Mutations ◽  
Healthy Controls ◽  
Brca1 And Brca2 ◽  
First Degree Relatives ◽  
Brca Gene ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations

Objective: Cancer ovary is one of the fatal gynecologic malignancies worldwide. Since breast cancer (BRCA) genes are considered tumor suppressor genes and play important roles in cancer by repairing of chromosomal damage with the error repair of DNA breaks. Therefore, breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations strongly enhance the development of ovarian cancer risk among women. Here, we report that both genes are an essential mediator of progress ovarian cancer, to determine the influence of BRCA1 and BRCA2 mutations in the improvement of ovarian cancer.Methods: A total of 25 subjects were chosen for the genetic studies, and three groups were recruited: fifteen ovarian cancer patients group, five healthy controls, and five first-degree relatives to a known case of ovarian cancer patients.Results: A genetic analysis revealed that a strong correlation exists between both gene mutations’ status in ovarian cancer, and BRCA gene mutations (185delAG, 5382insC, and 4153delA in BRCA1 and 6174delT in BRCA2) remained to establish to have a relatively high frequency among people in this study among ovarian cancer patients. Furthermore, seven patients with ovarian cancer carried all of the four investigated mutations, and five had three mutations.Conclusion: Otherwise, BRCA gene frequency showed low prevalence among first-degree relatives, and to a lesser extent among healthy controls, with only a few had all of the mutations combined. These data demonstrate for the first time a molecular link between BRCA1 and BRCA2 mutations in ovarian cancer progression in Iraq.

scholarly journals Circulating MicroRNAs in Blood and Other Body Fluids as Biomarkers for Diagnosis, Prognosis, and Therapy Response in Lung Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 421
Author(s):  
Luis Vicente Gayosso-Gómez ◽  
Blanca Ortiz-Quintero
Keyword(s):  
Lung Cancer ◽  
Clinical Application ◽  
Therapy Response ◽  
Body Fluids ◽  
Response To Treatment ◽  
Circulating Mirnas ◽  
Circulating Micrornas ◽  
Non Invasive ◽  
Potential Value ◽  
Potential Clinical Application

The identification of circulating microRNAs (miRNAs) in peripheral blood and other body fluids has led to considerable research interest in investigating their potential clinical application as non-invasive biomarkers of cancer, including lung cancer, the deadliest malignancy worldwide. Several studies have found that alterations in the levels of miRNAs in circulation are able to discriminate lung cancer patients from healthy individuals (diagnosis) and are associated with patient outcome (prognosis) and treatment response (prediction). Increasing evidence indicates that circulating miRNAs may function as mediators of cell-to-cell communication, affecting biological processes associated with tumor initiation and progression. This review is focused on the most recent studies that provide evidence of the potential value of circulating miRNAs in blood and other body fluids as non-invasive biomarkers of lung cancer in terms of diagnosis, prognosis, and response to treatment. The status of their potential clinical application in lung cancer is also discussed, and relevant clinical trials were sought and are described. Because of the relevance of their biological characteristics and potential value as biomarkers, this review provides an overview of the canonical biogenesis, release mechanisms, and biological role of miRNAs in lung cancer.

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