scholarly journals Biomarker-based early detection of epithelial ovarian cancer based on a five-protein signature in patient’s plasma – a prospective trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. Hasenburg ◽  
D. Eichkorn ◽  
F. Vosshagen ◽  
E. Obermayr ◽  
A. Geroldinger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Regression Model ◽  
Plasma Levels ◽  
Prospective Trial ◽  
Predictive Marker ◽  
Diagnostic Value ◽  
Ovarian Tumors ◽  
Link Type ◽  
Logistical Regression ◽  
Ovarian Masses

Abstract Background Trial on five plasma biomarkers (CA125, HE4, OPN, leptin, prolactin) and their possible role in differentiating benign from malignant ovarian tumors. Methods In this unicentric prospective trial preoperative blood samples of 43 women with ovarian masses determined for ovarian surgery were analyzed. 25 patients had pathologically confirmed benign, 18 malignant ovarian tumors. Blood plasma was analyzed for CA125, HE4, OPN, leptin, prolactin and MIF by multiplex immunoassay analysis. Each single protein and a logistical regression model including all the listed proteins were tested as preoperative predictive marker for suspect ovarian masses. Results Plasma CA125 was confirmed as a highly accurate tumor marker in ovarian cancer. HE4, OPN, leptin and prolactin plasma levels differed significantly between benign and malignant ovarian masses. With a logistical regression model a formula including CA125, HE4, OPN, leptin and prolactin was developed to predict malignant ovarian tumors. With a discriminatory AUC of 0.96 it showed to be a highly sensitive and specific diagnostic test for a malignant ovarian tumor. Conclusions The calculated formula with the combination of CA125, HE4, OPN, leptin and prolactin plasma levels surpasses each single marker in its diagnostic value to discriminate between benign and malignant ovarian tumors. The formula, applied to our patient population was highly accurate but should be validated in a larger cohort. Trial registration Clinical Trials.gov under NCT01763125, registered Jan. 8, 2013.

scholarly journals Comparison of conventional, doppler and contrast-enhanced ultrasonography in differential diagnosis of ovarian masses: a systematic review and meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e052830
Author(s):  
Lizhang Xun ◽  
Lamei Zhai ◽  
Hui Xu
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Data Extraction ◽  
Meta Analysis ◽  
Diagnostic Value ◽  
Doppler Us ◽  
Contrast Enhanced ◽  
Contrast Enhanced Ultrasonography ◽  
Sensitivity Specificity ◽  
Ovarian Masses

ObjectivesTo assess the value of conventional, Doppler and contrast-enhanced ultrasonography (CEUS) (conventional ultrasonography (US), Doppler US and CEUS) for diagnosing ovarian cancer.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase and the Cochrane Library were conducted for studies published until October 2021.Eligibility criteriaStudies assessed the diagnostic value of conventional US, Doppler US or CEUS for detecting ovarian cancer, with no restrictions placed on published language and status.Data extraction and synthesisThe study selection and data extraction were performed by two independent authors. The sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), diagnostic OR (DOR) and area under the receiver operating characteristic curve (AUC) were pooled using the bivariate generalised linear mixed model and random effects model.ResultsThe meta-analysis included 72 studies and involved 9296 women who presented with ovarian masses. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC for conventional US were 0.91 (95% CI: 0.87 to 0.94) and 0.87 (95% CI: 0.82 to 0.91), 6.87 (95% CI: 4.98 to 9.49) and 0.10 (95% CI: 0.07 to 0.15), 57.52 (95% CI: 36.64 to 90.28) and 0.95 (95% CI: 0.93 to 0.97), respectively. The sensitivity, specificity, PLR, NLR, DOR and AUC for Doppler US were 0.93 (95% CI: 0.91 to 0.95) and 0.85 (95% CI: 0.80 to 0.89), 6.10 (95% CI: 4.59 to 8.11) and 0.08 (95% CI: 0.06 to 0.11), 61.76 (95% CI: 39.99 to 95.37) and 0.96 (95% CI: 0.94 to 0.97), respectively. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC for CEUS were 0.97 (95% CI: 0.92 to 0.99) and 0.92 (95% CI: 0.85 to 0.95), 11.47 (95% CI: 6.52 to 20.17) and 0.03 (95% CI: 0.01 to 0.09), 152.11 (95% CI: 77.77 to 297.51) and 0.99 (95% CI: 0.97 to 0.99), respectively. Moreover, the AUC values for conventional US (p=0.002) and Doppler US (p=0.005) were inferior to those of CEUS.ConclusionsConventional US, Doppler US and CEUS have a relatively high differential diagnostic value for differentiating between benign and malignant ovarian masses. The diagnostic performance of CEUS was superior to that of conventional US and Doppler US.

scholarly journals Circulating markers of neutrophil extracellular traps (NETs) in patients with ovarian tumors

2021 ◽  
Author(s):  
Arturas Dobilas ◽  
Charlotte Thålin ◽  
Håkan Wallén ◽  
Christer Borgfeldt
Keyword(s):  
Ovarian Cancer ◽  
Plasma Levels ◽  
Neutrophil Extracellular Traps ◽  
Ovarian Tumors ◽  
Ca 125 ◽  
Benign Tumors ◽  
Tumor Type ◽  
Cox Regression Analysis ◽  
Adnexal Masses ◽  
Extracellular Traps

Abstract Background Inflammation is a hallmark of cancer, and emerging light is being shed on the neutrophil release of nuclear chromatin, referred to as neutrophil extracellular traps (NETs) in cancer and cancer associated thrombosis. The NET-specific marker citrullinated histone H3 (H3Cit) has been found to be elevated in plasma from patients with malignancies, suggesting the potential of NET markers, such as H3Cit, as novel cancer biomarkers. Objective To determine the levels of plasma H3Cit in blood in women with adnexal masses. Subjects and Method s: Peripheral blood samples were obtained preoperatively from 199 patients admitted for primary surgery of adnexal masses 2015–2017. Patients were grouped according to tumor type and stage of cancer. Plasma levels of H3Cit-DNA, cell free DNA (cfDNA) and the clinically implemented tumor marker cancer antigen 125 (CA125) were determined with ELISA. Results Plasma levels of H3Cit-DNA and cfDNA were not elevated in women with borderline or malignant ovarian tumors compared with women with benign tumors. Increased plasma levels of CA125 were detected in borderline and ovarian cancer stage I and stage II-IV compared with benign ovarian tumor patients (ptrend<0.001). In Cox regression analysis high levels of Ca 125 dichotomized at 326 IU/ml (median) showed worse overall survival hazard ratio 1.9 (95 % C.I. 1.03–3.36; p = 0.038). No differences were found in the survival analyses in malignant ovarian tumors analyzing the cfDNA and H3Cit-DNA levels. Conclusion This study did not find any association nor prognostic association between the plasma levels of the NET marker H3Cit and ovarian cancer patients.

Diagnostic Value of International Ovarian Tumor Analysis Simple Rules (IOTA-SR) In Iranian Patients with Ovarian Mass

2021 ◽  
Vol 15 (5) ◽  
pp. 1647-1651
Author(s):  
Mohammad Reza Babaei ◽  
Mohammadreza Khaleghi ◽  
Manizhe Ataee Kachuee ◽  
Farnaz Ardiyani ◽  
Setare Nassiri
Keyword(s):  
Ovarian Cancer ◽  
Likelihood Ratio ◽  
Predictive Value ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Diagnostic Value ◽  
Ovarian Tumors ◽  
Benign Tumors ◽  
Ovarian Mass ◽  
Iranian Patients

Background: Among gynecologic malignancies, ovarian cancer has the highest mortality rate per case. The most important prognostic feature of ovarian cancer is an early diagnosis. The IOTA-SR is an ultrasound exam criterion for classifying benign or malignant ovarian tumors, which could be used effectively by an inexperienced radiologist. This study aimed to evaluate the diagnostic value of IOTA-SR in Iranian patients with ovarian tumors. Methods: In this cross-sectional study, considering inclusion and exclusion criteria, 60 females enrolled (from 2019-1 to 2019-12). Patients were evaluated with ultrasound by an experienced radiologist. Tumors were classified, as benign or malignant according to the IOTA-SR criteria. After laparotomy, histological and ultrasond examination findings were compared. Results: According to histopathologic results, the prevalence of malignancy was 63.3% (38 malignant and 22 benign tumors). The IOTA-SR could be applied in all the participants as 21 tumors (35%) were classified as benign and 39 (65%) as malignant. Compared with histopathologic results, the IOTA-SR yielded 36 true positives, three false positives, 19 true negatives, and two false negatives. Thus, assessing ovarian mass using IOTA-SR achieved a sensitivity of 94.7%, a specificity of 86.3%, a positive predictive value of 92.3%, a negative predictive value of 90.47%, positive likelihood ratio of 6.91, negative likelihood ratio of 0.091, overall accuracy of 91.6%, and kappa coefficient of 0.819 (P<0.001). Conclusions: IOTA-SR criteria have a high diagnostic value in differentiation of the malignant and benign ovarian tumors and can be applied in daily practice.

Human Kallikrein 5: An Interesting Novel Biomarker in Ovarian Cancer Patients that Elicits a Humoral Response

2009 ◽  
Vol 24 (3) ◽  
pp. 211-211
Author(s):  
Elisabetta Bandiera ◽  
Laura Zanotti ◽  
Eliana Bignotti ◽  
Chiara Romani ◽  
Renata Tassi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Immune Complexes ◽  
Tumor Antigens ◽  
Gynecological Cancer ◽  
Sandwich Elisa ◽  
Ovarian Tumors ◽  
Borderline Tumors ◽  
Healthy Women ◽  
Ovarian Masses

Background and aim Epithelial ovarian cancer (EOC) is characterized by few early symptoms, presentation at an advanced stage and poor survival. As a result, it is the most frequent cause of death from gynecological cancer. Recently, not only tumor antigens but also antibodies produced in response to the disease have been considered as biomarkers for early detection of EOC. Kallikrein-related peptidases (KLK) are secreted serine proteases implicated in tumor progression. A recent study has demonstrated that the serum KLK5 (sKLK5) concentration is elevated in patients with EOC, but the existence of a humoral immune response to KLK5 has not been studied. Moreover, the presence of sKLK5 in other ovarian diseases has not been clearly determined. The aim of this study was to examine the serological existence of anti-KLK5 antibodies, bound to KLK5 into circulating immune complexes (KLK5-lgM and KLK5-lgG ICs) or free antibodies (IgM and IgG), in healthy women and in patients with benign ovarian masses, borderline tumors and EOC. In the same patients we also assessed the levels of sKLK5. Materials and methods Serum samples were obtained from 50 healthy women, 50 patients with benign ovarian masses, 1 7 patients with borderline ovarian tumors, and 50 patients with EOC, before any surgical or chemotherapeutic treatment. Patients with a past or concomitant history of malignancy were excluded from the study. KLK5-lgM and KLK5-lgG ICs were detected with a sandwich ELISA using a polyclonal anti-KLK5 antibody (R&D Systems, Minneapolis, MN, USA) in capture and an anti-hlgM-HRP antibody (Sigma Aldrich Inc, St Louis, MO, USA) or anti-hlgG-HRP antibody (Sigma) in detection. Free anti-KLK5 IgM and IgG were detected with an indirect ELISA using recombinant human kallikrein 5 (R&D) in coating and anti-hlgM-HRP or anti-hlgG-HRP antibodies in detection. Finally, sKLK5 was detected with a sandwich ELISA, using a polyclonal anti-KLK5 antibody in capture and a biotinylated poyclonal anti-hK5 antibody (R&D) in detection. Results Elevated levels of KLK5-lgM and KLK5-lgG ICs were detected in 11% of patients with borderline tumors and 8% of patients with EOC, whereas elevated levels of free anti-KLK5 IgM and IgG were found in 1 7% of patients with borderline tumors and 8% of patients with EOC, resulting in a 100% specificity both in healthy women and patients with benign ovarian disease. Patients with EOC showed higher levels of sKLK5, whereas the protein was almost undetectable in women with other ovarian tumors (Kruskal-Wallis test: p<0.001). In particular, at 95% specificity in healthy controls, 52% of patients with EOC showed high sKLK5 levels. Interestingly, both the immune complexes and the free antibodies were elevated in patients with undetectable sKLK5 levels and borderline tumors with intraepithelial carcinoma. Conclusion Our results showed that sKLK5 is a potential new biomarker to be used in combination with other biomarkers for EOC detection. Moreover, the combination of sKLK5 and antibodies reactive to KLK5 might improve the sensitivity in EOC detection since these antibodies may be found in patients without detectable sKLK5 levels. In conclusion, the identification of an immune response that generally precedes the presence of high levels of circulating antigens may represent a novel useful tool for early EOC detection.

scholarly journals Plasma Levels of High-Mobility Group Box 1 during Peptide Vaccination in Patients with Recurrent Ovarian Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Kayoko Waki ◽  
Kouichiro Kawano ◽  
Naotake Tsuda ◽  
Kimio Ushijima ◽  
Kyogo Itoh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Plasma Levels ◽  
High Mobility ◽  
Suppressor Cell ◽  
Recurrent Ovarian Cancer ◽  
High Mobility Group ◽  
Peptide Vaccination ◽  
Clinical Trial Registry ◽  
Chi Square ◽  
Link Type

High-mobility group box 1 (HMGB1) is a nuclear protein that is known to be secreted into extracellular fluids from injured cells, activated macrophages, and tumor cells. The clinical correlation of circulating HMGB1 levels with various diseases including cancer has been reported. However, there is no information on HMGB1 levels in cancer patients treated with peptide vaccination. In the present study, we investigated the plasma levels of HMGB1 during personalized peptide vaccination in patients with recurrent ovarian cancer. Frozen plasma samples of 39 patients from previously conducted clinical trials were used in this study. HMGB1 levels were decreased after the 1st cycle of vaccination from their prevaccination levels. However, no correlation was observed between HMGB1 and overall survival (OS). The correlation between plasma HMGB1 levels and other biomarker levels was further analyzed by scatter plot, revealing that HMGB1 levels after the 1st cycle of vaccination were significantly correlated with myeloid-derived suppressor cell (MDSC) frequency after the 1st cycle of vaccination (r=0.357, p=0.032). Chi-square test showed that epitope spreading was significantly related with changes of HMGB1 (p=0.030). These results suggest that plasma HMGB1 is a possible biomarker for cancer vaccine therapy, although direct correlation with OS has not been obtained. This trial is registered with Clinical Trial Registry under trial numbers UMIN000003083 and UMIN000001482.

scholarly journals Diagnostic value of [18F]FDG PET/MRI for staging in patients with ovarian cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hideaki Tsuyoshi ◽  
Tetsuya Tsujikawa ◽  
Shizuka Yamada ◽  
Hidehiko Okazawa ◽  
Yoshio Yoshida
Keyword(s):  
Ovarian Cancer ◽  
Fdg Pet ◽  
Diagnostic Value ◽  
Mri Contrast ◽  
Diagnostic Potential ◽  
Contrast Enhanced Ct ◽  
Contrast Enhanced ◽  
Imaging Results ◽  
N Stage ◽  
Sensitivity Specificity

Abstract Purpose To evaluate the diagnostic potential of PET/MRI with 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) in ovarian cancer. Materials and methods Participants comprised 103 patients with suspected ovarian cancer underwent pretreatment [18F]FDG PET/MRI, contrast-enhanced CT (ceCT) and pelvic dynamic contrast-enhanced MRI (ceMRI). Diagnostic performance of [18F]FDG PET/MRI and ceMRI for assessing the characterization and the extent of the primary tumor (T stage) and [18F]FDG PET/MRI and ceCT for assessing nodal (N stage) and distant (M stage) metastases was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. The McNemar test was employed for statistical analysis. Results Accuracy for the characterization of suspected ovarian cancer was significantly better for [18F]FDG PET/MRI (92.5%) [95% confidence interval (CI) 0.84–0.95] than for ceMRI (80.6%) (95% CI 0.72–0.83) (p < 0.05). Accuracy for T status was 96.4% (95% CI 0.96–0.96) and 92.9% (95% CI 0.93–0.93) for [18F]FDG PET/MRI and ceMRI/ceCT, respectively. Patient-based accuracies for N and M status were 100% (95% CI 0.88–1.00) and 100% (95% CI 0.88–1.00) for [18F]FDG PET/MRI and 85.2% (95% CI 0.76–0.85) and 30.8% (95% CI 0.19–0.31) for ceCT and M staging representing significant differences (p < 0.01). Lesion-based sensitivity, specificity and accuracy for N status were 78.6% (95% CI 0.57–0.91), 95.7% (95% CI 0.93–0.97) and 93.9% (95% CI 0.89–0.97) for [18F]FDG PET/MRI and 42.9% (95% CI 0.24–0.58), 96.6% (95% CI 0.94–0.98) and 90.8% (95% CI 0.87–0.94) for ceCT. Conclusions [18F]FDG PET/MRI offers better sensitivity and specificity for the characterization and M staging than ceMRI and ceCT, and diagnostic value for T and N staging equivalent to ceMRI and ceCT, suggesting that [18F]FDG PET/MRI might represent a useful diagnostic alternative to conventional imaging modalities in ovarian cancer.

scholarly journals Allogeneic human neural stem cells for improved therapeutic delivery to peritoneal ovarian cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rachael Mooney ◽  
Wafa Abidi ◽  
Jennifer Batalla-Covello ◽  
Hoi Wa Ngai ◽  
Caitlyn Hyde ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Tracking ◽  
Scale Up ◽  
Cancer Therapeutics ◽  
Cost Effective ◽  
Tumor Stroma ◽  
Clinical Safety ◽  
Peritoneal Cancer ◽  
Human Neural Stem Cells ◽  
Link Type

Abstract Background Immortalized, clonal HB1.F3.CD21 human neural stem/progenitor cells (NSCs), loaded with therapeutic cargo prior to intraperitoneal (IP) injection, have been shown to improve the delivery and efficacy of therapeutic agents in pre-clinical models of stage III ovarian cancer. In previous studies, the distribution and efficacy of the NSC-delivered cargo has been examined; however, the fate of the NSCs has not yet been explored. Methods To monitor NSC tropism, we used an unconventional method of quantifying endocytosed gold nanorods to overcome the weaknesses of existing cell-tracking technologies. Results Here, we report efficient tumor tropism of HB1.F3.CD21 NSCs, showing that they primarily distribute to the tumor stroma surrounding individual tumor foci within 3 h after injection, reaching up to 95% of IP metastases without localizing to healthy tissue. Furthermore, we demonstrate that these NSCs are non-tumorigenic and non-immunogenic within the peritoneal setting. Conclusions Their efficient tropism, combined with their promising clinical safety features and potential for cost-effective scale-up, positions this NSC line as a practical, off-the-shelf platform to improve the delivery of a myriad of peritoneal cancer therapeutics.

scholarly journals Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e041463
Author(s):  
Anita Mansouri ◽  
Naomi McGregor ◽  
Rachel Dunn ◽  
Sam Dobbie ◽  
Jane Holmes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Antiangiogenic Therapy ◽  
Single Agent ◽  
Unmet Need ◽  
Dropout Rate ◽  
Weekly Paclitaxel ◽  
Type I ◽  
Link Type ◽  
Platinum Based Chemotherapy

IntroductionPatients relapsing within 12 months of platinum-based chemotherapy usually have a poorer response to subsequent treatments. To date, extensive research into the mechanism of resistance to platinum agents in the treatment of ovarian cancer has not resulted in improved responses or longer survival. Further experimental work and clinical trials with novel agents are therefore justified to address this unmet need.Patients with ovarian, fallopian tube or primary peritoneal cancer that has relapsed within 12 months of platinum-based chemotherapy will be randomised with stratification for BReast CAncer gene (BRCA) status, prior poly (ADP-ribose) polymerase (PARP) exposure and prior antiangiogenic therapy into weekly paclitaxel (chemotherapy), olaparib or the combination of cediranib and olaparib. They will be followed until disease progression or unacceptable toxicity develops. Our trial design permits two investigations. We will compare the efficacy and tolerability of single-agent olaparib with weekly paclitaxel. We will also compare the efficacy and tolerability of olaparib with the combination of olaparib and cediranib. The required sample size of 138 participants (46 per arm) was calculated using a 20% one-sided type I error, 80% power and 15% dropout rate. Recruitment will last 34 months with a follow-up of 18 months.Methods and analysisEthics and disseminationThis study will be conducted under a UK Medicines and Healthcare Products Regulatory Agency Clinical Trials Authorisation. Approval to conduct the study was obtained from the responsible authority before beginning the study. The sponsor will retain ownership of all data arising from the trial. We aim to publish this research in a specialist peer-reviewed scientific journal on study completion. EudraCT number: 2016-000559-28, ethics reference number: 16/LO/2150.Trial registration numberISRCTN: ISRCTN14784018, clinicaltrials.gov: NCT03117933; Pre-results.

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