Early Detection Of Ovarian Cancer Research Articles

Characterization of the Electrochemical Detection of NG-Hydroxy-L-Arginine

NG-Hydroxy-L-arginine (NOHA) is a suspected biomarker in breast cancer due to its involvement in the L-arginine metabolism [1]. Previous research in human breast cancer cells has shown that NOHA, a potent arginase inhibitor, has an antiproliferative and apoptotic actions on the arginase-expressing cells [1]. NOHA is a stable intermediate product in the production of NO from the consumption of L-arginine [1]. L-ornithine and L-citrulline are also involved in the metabolism of L-arginine through the urea cycle; the urea cycle has been known to be disrupted in cancer patients [1]. Early detection of cancer is important for rapid treatment options to be available [2]. Electrochemical detection is an established, cost-effective method that has potential to detect the onset of cancer because of its ability to successfully detect low levels of analyte concentrations. Before a robust biosensor sensor can be made the characterization of the electrochemical detection of NOHA needs to be done. Electrochemical activity of NOHA was investigated with cyclic voltammetry and differential pulse voltammetry. NOHA was found to have an oxidation and reduction peak at 355 mV and 188 mV vs. Ag/AgCl respectively. In cyclic voltammetric measurements a scan rate of 50 mVs-1 was used over the applied potential of -0.2 to 0.6 V vs Ag/AgCl. Triplicate data was obtained for serial dilutions of NOHA in two different buffers; Phosphate Buffer Saline solution pH 7.3 (PBS) and 100uM L-Ornithine, 10uM L-Citrulline, and 100uM L-Arginine in PBS (LOCA). The electrochemical detection of NOHA in a LOCA solution was done to understand the effect of a urea cycle metabolite mixture on electrode fowling and sensitivity. A shift in oxidation peak voltage was found for the LOCA solution by 5 mV to 360 mV. The sensitivity of the NOHA in PBS and LOCA solutions were found to be 5.4 nA/uM and 4.8 nA/uM respectively. In addition to our multiple data points to discuss sensitivity and reproducibility in the detection of NOHA, we will report kinetic information including the number of electrons transferred and diffusivity. We will also discuss our progress to decrease the limit-of-detection of NOHA in an effort to make a more sensitive bioanalyte sensor. [1] R. Singh, S. Pervin, A. Karimi, S. Cederbaum, and G. Chaudhuri, “Arginase activity in human breast cancer cell lines: Nω-hydroxy-L-arginine selectively inhibits cell proliferation and induces apoptosis in MDA-MB-468 cells,” Cancer Res., vol. 60, pp. 3305–3312, (2000) [2] Zhen Zhang, Robert C. Bast, Jr., Yinhua Yu, Jinong Li, Lori J. Sokoll, Alex J. Rai, Jason M. Rosenzweig, Bonnie Cameron, Young Y. Wang, Xiao-Ying Meng, Andrew Berchuck, Carolien van Haaften-Day, and Neville F. Hacker, Henk W. A. de Bruijn, Ate G. J. van der Zee, Ian J. Jacobs, Eric T. Fung, and D. W. Chan, “Three Biomarkers Identified from Serum Proteomic Analysis for the Detection of Early Stage Ovarian Cancer,” Cancer Res., vol. 64, pp. 5882–5890, (2004)

Ovarian cancer screening with the Risk of Ovarian Cancer Algorithm (ROCA): Good, bad, or just expensive?

ObjectivesTo measure the effectiveness of ovarian cancer screening using the Risk of Ovarian Cancer Algorithm (ROCA). MethodsA Markov model was constructed based on the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). This model was used to predict the outcome of ovarian cancer screening with ROCA. ResultsThe model predicted the ovarian cancer mortality from age 50 to age 85 to be 0.954% with a decrease in life expectancy of 0.178years (yrs) per person. Using data from the UKCTOCS the model predicted a similar reduction in mortality (11% vs. 10%), and similar curves for ovarian cancer mortality. Screening at age 50 for 20yrs reduced ovarian cancer mortality from 0.953% to 0.898%, an absolute decrease of 6%, yielding an increase in life expectancy of 0.0101yrs, preventing 55 deaths per 100,000 screened at a cost of $585,946 per life-yr. Screening for 30yrs reduced mortality from 0.954% to 0.872%, an absolute decrease of 9%, preventing 82 deaths at a cost of $763,970 per life-yr. ConclusionThe ROCA test can improve the detection of early ovarian cancer but is not practical for screening in an average-risk population. We predict the ROCA test will reduce overall ovarian cancer mortality by 6% to 9% but at a substantial cost. For ROCA to be practical, the cost would need to be reduced ten-fold and would have only a marginal impact on mortality from ovarian cancer. This model supports the FDA's criticism of the ROCA test.Ovarian cancer screening may reduce mortality from ovarian cancer but is not cost effective.

A Comprehensive Review of the Diagnostic and Treatment Methods for Ovarian Cancer

Ovarian cancer is amongst the most life-threatening malignancy of the female reproductive system, whereas 90% of those ovarian cancers are epithelial with an overall poor five-year survival rate of 44% across all stages and all races [1]–[2], [31]. This paper aims to review the current treatment and diagnostic strategies for ovarian cancer [3]. Using grounded substantial research, multiple figures were developed to show the relations of ovarian cancer diagnostics and ovarian cancer therapeutics. It is a great start to look into what may be causing most patients to become resistant to the current standard of care, platinum-based chemotherapeutics, for ovarian cancer [4]. A comprehensive literature review will be used to understand the genetic basis of the disease and possible cancer growth patterns, so we could possibly introduce better diagnostics and therapeutics [5]. The findings show that there are a variety of treatments options other than the standard of care, platinum-based therapy [6]. Nanoparticle encapsulation therapy is one way that has been approved by the FDA to therapeutically treat ovarian cancer without the platinum resistant side effects [7]. Also, the discovery of different diagnostics for ovarian cancer can help with better individualized treatments for patients with different forms of ovarian cancer [8]. Currently, the only serous diagnostic test for the detection of ovarian cancer is high levels of Cancer Antigen 125 (CA-125), which is only shown in 50% of early staged ovarian cancers [16]. The main treatment option for ovarian cancer is platinum-based drugs, in which most cases of patients with ovarian cancer will become resistant. Detecting and treating ovarian cancer while the cells are small, contained, and still in the early stages in vivo still remains to be a challenge [9]. Here, we will demonstrate the bioelectrical interactions of the ovarian cancer cells fused with the magnetic iron oxide nanoparticles with the use of an MRI. The findings demonstrate that the diagnostic method for the early detection of epithelial ovarian cancer requires the use of magnetic iron oxide nanoparticles with specific ligand external profiles as a contrast reagent to make the small-sized ovarian cancer cells appear more visible under MRI.

A Comprehensive Review of the Diagnostic and Treatment Methods for Ovarian Cancer

Ovarian cancer is amongst the most life-threatening malignancy of the female reproductive system, whereas 90% of those ovarian cancers are epithelial with an overall poor five-year survival rate of 44% across all stages and all races [1]–[2], [31]. This paper aims to review the current treatment and diagnostic strategies for ovarian cancer [3]. Using grounded substantial research, multiple figures were developed to show the relations of ovarian cancer diagnostics and ovarian cancer therapeutics. It is a great start to look into what may be causing most patients to become resistant to the current standard of care, platinum-based chemotherapeutics, for ovarian cancer [4]. A comprehensive literature review will be used to understand the genetic basis of the disease and possible cancer growth patterns, so we could possibly introduce better diagnostics and therapeutics [5]. The findings show that there are a variety of treatments options other than the standard of care, platinum-based therapy [6]. Nanoparticle encapsulation therapy is one way that has been approved by the FDA to therapeutically treat ovarian cancer without the platinum resistant side effects [7]. Also, the discovery of different diagnostics for ovarian cancer can help with better individualized treatments for patients with different forms of ovarian cancer [8]. Currently, the only serous diagnostic test for the detection of ovarian cancer is high levels of Cancer Antigen 125 (CA-125), which is only shown in 50% of early staged ovarian cancers [16]. The main treatment option for ovarian cancer is platinum-based drugs, in which most cases of patients with ovarian cancer will become resistant. Detecting and treating ovarian cancer while the cells are small, contained, and still in the early stages in vivo still remains to be a challenge [9]. Here, we will demonstrate the bioelectrical interactions of the ovarian cancer cells fused with the magnetic iron oxide nanoparticles with the use of an MRI. The findings demonstrate that the diagnostic method for the early detection of epithelial ovarian cancer requires the use of magnetic iron oxide nanoparticles with specific ligand external profiles as a contrast reagent to make the small-sized ovarian cancer cells appear more visible under MRI.

Cell-free DNA methylation patterns for early detection and management of ovarian and breast cancers

Cell-free DNA methylation patterns for early detection and management of ovarian and breast cancers

Clinical significance of promoter hypermethylation of genes in ovarian cancer

// Xinxin Zhu 1, 2 and Jinghe Lang 1 1 Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China 2 Department of Obstetrics and Gynecology, Institute for Wound Research, University of Florida, Gainesville, Florida, USA Correspondence to: Jinghe Lang, email: langjh@hotmail.com , doctorlangjh@163.com Keywords: epigenetic; DNA methylation; gene silencing; immunotherapy; ovarian cancer Received: August 02, 2017      Accepted: December 18, 2017      Published: December 29, 2017 ABSTRACT Ovarian cancer is the most lethal condition in gynecologic oncology. The known prognostic factors for ovarian cancer include tumor stage, histological grade, lymph node, and distant metastasis; however, handy and reliable molecular biomarkers for prevention, diagnosis, personalized treatment, and prognosis are scarce. Despite histological differences, the clinical treatment strategy is similar for ovarian cancers. The survival rate for ovarian cancer, however, remains relatively low. Accumulating evidence suggests that hypermethylated promoters of genes can be promising candidates as molecular biomarkers in ovarian cancer risk evaluation, early detection, personalized treatment, and prognosis. With advancements in immunology, hypermethylation of gene promoters was found to alter the tumor immune microenvironment, and gene methyltransferase inhibitors can contribute to ovarian cancer immunotherapy by boosting tumor immunogenicity and immune response and decreasing immunosuppression. Although DNMTis demonstrate high efficacy in hematologic malignancies, the application of DNMTis in solid tumors is just in its beginning. This article, drawing on both preclinical and clinical data, systematically reviews the common hypermethylated genes in ovarian cancer and their clinical applications, evaluating their usefulness in early diagnosis, personalized treatment, prognosis prediction, and the establishment of combined therapy of methyltransferase inhibitors and immunotherapy.

Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels: Results from the EPIC cohort.

CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76-0.92]; lowest tertile: 0.76 [0.67-0.86]; phet = 0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection.

The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer

BackgroundDespite a myriad of attempts in the last three decades to diagnose ovarian cancer (OC) earlier, this clinical aim still remains a significant challenge. Aberrant methylation patterns of linked CpGs analyzed in DNA fragments shed by cancers into the bloodstream (i.e. cell-free DNA) can provide highly specific signals indicating cancer presence.MethodsWe analyzed 699 cancerous and non-cancerous tissues using a methylation array or reduced representation bisulfite sequencing to discover the most specific OC methylation patterns. A three-DNA-methylation-serum-marker panel was developed using targeted ultra-high coverage bisulfite sequencing in 151 women and validated in 250 women with various conditions, particularly in those associated with high CA125 levels (endometriosis and other benign pelvic masses), serial samples from 25 patients undergoing neoadjuvant chemotherapy, and a nested case control study of 172 UKCTOCS control arm participants which included serum samples up to two years before OC diagnosis.ResultsThe cell-free DNA amount and average fragment size in the serum samples was up to ten times higher than average published values (based on samples that were immediately processed) due to leakage of DNA from white blood cells owing to delayed time to serum separation. Despite this, the marker panel discriminated high grade serous OC patients from healthy women or patients with a benign pelvic mass with specificity/sensitivity of 90.7% (95% confidence interval [CI] = 84.3–94.8%) and 41.4% (95% CI = 24.1–60.9%), respectively. Levels of all three markers plummeted after exposure to chemotherapy and correctly identified 78% and 86% responders and non-responders (Fisher’s exact test, p = 0.04), respectively, which was superior to a CA125 cut-off of 35 IU/mL (20% and 75%). 57.9% (95% CI 34.0–78.9%) of women who developed OC within two years of sample collection were identified with a specificity of 88.1% (95% CI = 77.3–94.3%). Sensitivity and specificity improved further when specifically analyzing CA125 negative samples only (63.6% and 87.5%, respectively).ConclusionsOur data suggest that DNA methylation patterns in cell-free DNA have the potential to detect a proportion of OCs up to two years in advance of diagnosis and may potentially guide personalized treatment. The prospective use of novel collection vials, which stabilize blood cells and reduce background DNA contamination in serum/plasma samples, will facilitate clinical implementation of liquid biopsy analyses.

In Vivo Optical Detection and Spectral Triangulation of Carbon Nanotubes.

In the first in vivo demonstration of spectral triangulation, biocompatible composites of single-walled carbon nanotubes in Matrigel have been surgically implanted into mouse ovaries and then noninvasively detected and located. This optical method deduces the three-dimensional position of a short-wave IR emission source from the wavelength-dependent attenuation of fluorescence in tissues. Measurements were performed with a second-generation optical scanner that uses a light-emitting diode matrix emitting at 736 nm for diffuse specimen excitation. The intrinsic short-wave IR fluorescence of the nanotubes was collected at various positions on the specimen surface, spectrally filtered, and detected by a photon-counting InGaAs avalanche photodiode. Sensitivity studies showed a detection limit of ∼120 pg of nanotubes located beneath ∼3 mm of tissue. In addition, the mass and location of implanted nanotubes could be deduced through spectral triangulation with sub-millimeter accuracy, as validated with the aid of magnetic resonance imaging (MRI) data. Dual-modality imaging combining spectral triangulation with computed tomography or MRI will allow accurate registration of emission centers with anatomical features. These results are a step toward the future use of probes with targeting agents such as antibodies linked to nanotube tags for the noninvasive detection and imaging of tumors in preclinical research on small animals. Translation to the clinic could aid in early detection of ovarian cancer and identification of metastases for resection during primary surgery.

A novel algorithm to improve specificity in ovarian cancer detection

BackgroundMeasurement of autoantibodies (AAbs) to tumor associated antigens has been proposed to aid in the early detection of ovarian cancer with high specificity. Here we describe a multiplex approach to evaluate selected peptide epitopes of p53 protein, and propose a novel approach to increase specificity and potentially sensitivity for discrimination between healthy women and women with cancerous masses. Materials and methods20-mer overlapping peptide epitopes of p53, generated by mapping the complete p53 sequence, were evaluated in a multiplex immunoassay for their detection of serum AAbs in patients with ovarian cancer, using Luminex technology. AAbs to the selected peptides and to p53 full length protein were then detected in a multiplex immunoassay evaluating 359 sera from healthy women and 285 sera from patients with early and late stage ovarian cancer. CA-125 levels were measured in all p53 AAb-positive sera. ResultsWe considered the AAb results together to identify sera where both the full length protein and at least one selected peptide epitope were positive and chose cutoffs that reduced false positives from these AAbs to 1/359 samples, improving specificity. Using this combined approach, we could identify 7 AAb-positive patients that were negative for CA-125 (concentrations below 35 IU/mL); this represents 26% of the p53 positive patients in the total population. ConclusionBy detecting p53 AAbs in CA-125-negative sera, we demonstrated that combining measurement of AAbs to the full length p53 protein and one or more selected epitopes can potentially improve sensitivity and specificity for ovarian cancer detection.

Ovarian Cancer Prevention, Screening, and Early Detection: Report From the 11th Biennial Ovarian Cancer Research Symposium.

The aim of this study is to provide a summary report on recent research advances in ovarian cancer prevention, screening, and early detection that were presented at the 11th Biennial Ovarian Cancer Research Symposium in Seattle, Wash. At the symposium, researchers from around the world participated in the poster, invited oral presentation and keynote presentation, and discussed the latest advances in the areas of cancer prevention, screening, and early detection. In the Scientific Session for Prevention, Screening, and Early Detection, Usha Menon, PhD (University of College London), presented exploratory studies from the ongoing UK Collaborative Trial of Ovarian Cancer Screening trial. Karen Lu, MD, presented her studies on BRCA testing and salpingectomies as prevention strategies. Eight speakers were selected from the abstracts for short oral presentations, and the topic ranges from Ovarian Cancer Early Detection Program by Saul Rivkin, MD, to the ultra-deep sequencing of somatic mutations in TP53 in normal and cancer patients by Rosana Risques, PhD. Fourteen additional poster presentations, ranging from the potential role of cancer stem cells in recurrence to retrotransposons in ovarian cancer development, round up the session. Although progress is being made in the areas of prevention, screening, and early detection, these advances have not yet translated into tangible clinical benefits for patients with ovarian cancer. A wide array of research topics presented in the session provides a glimmer of hope that better understanding of genetic risk factors, refining screening strategies, and developing new methods for early detection will eventually lead to improved outcome for patients with ovarian cancer.

A combination of circulating miRNAs for the early detection of ovarian cancer.

Ovarian cancer is the leading cause of gynecologic cancer mortality, due to the difficulty of early detection. Current screening methods lack sufficient accuracy, and it is still challenging to propose a new early detection method that improves patient outcomes with less-invasiveness. Although many studies have suggested the utility of circulating microRNAs in cancer detection, their potential for early detection remains elusive. Here, we develop novel predictive models using a combination of 8 circulating serum miRNAs. This method was able to successfully distinguish ovarian cancer patients from healthy controls (area under the curve, 0.97; sensitivity, 0.92; and specificity, 0.91) and early-stage ovarian cancer from patients with benign tumors (0.91, 0.86 and 0.83, respectively). This method also enables subtype classification in 4 types of epithelial ovarian cancer. Furthermore, it is found that most of the 8 miRNAs were packaged in extracellular vesicles, including exosomes, derived from ovarian cancer cells, and they were circulating in murine blood stream. The circulating miRNAs described in this study may serve as biomarkers for ovarian cancer patients. Early detection and subtype determination prior to surgery are crucial for clinicians to design an effective treatment strategy for each patient, as is the goal of precision medicine.

Committee Opinion No. 716 Summary: The Role of the Obstetrician-Gynecologist in the Early Detection of Epithelial Ovarian Cancer in Women at Average Risk.

Ovarian cancer is the second most common type of female reproductive cancer, and more women die from ovarian cancer than from cervical cancer and uterine cancer combined. Currently, there is no strategy for early detection of ovarian cancer that reduces ovarian cancer mortality. Taking a detailed personal and family history for breast, gynecologic, and colon cancer facilitates categorizing women based on their risk (average risk or high risk) of developing epithelial ovarian cancer. Women with a strong family history of ovarian, breast, or colon cancer may have hereditary breast and ovarian cancer syndrome (BRCA mutation) or hereditary nonpolyposis colorectal cancer (Lynch syndrome), and these women are at increased risk of developing ovarian cancer. Women with these conditions should be referred for formal genetic counseling to better assess their cancer risk, including their risk of ovarian cancer. If appropriate, these women may be offered additional testing for early detection of ovarian cancer. The use of transvaginal ultrasonography and tumor markers (such as cancer antigen 125), alone or in combination, for the early detection of ovarian cancer in average-risk women have not been proved to reduce mortality, and harms exist from invasive diagnostic testing (eg, surgery) resulting from false-positive test results. The patient and her obstetrician-gynecologist should maintain an appropriate level of suspicion when potentially relevant signs and symptoms of ovarian cancer are present.

Committee Opinion No. 716: The Role of the Obstetrician-Gynecologist in the Early Detection of Epithelial Ovarian Cancer in Women at Average Risk.

Ovarian cancer is the second most common type of female reproductive cancer, and more women die from ovarian cancer than from cervical cancer and uterine cancer combined. Currently, there is no strategy for early detection of ovarian cancer that reduces ovarian cancer mortality. Taking a detailed personal and family history for breast, gynecologic, and colon cancer facilitates categorizing women based on their risk (average risk or high risk) of developing epithelial ovarian cancer. Women with a strong family history of ovarian, breast, or colon cancer may have hereditary breast and ovarian cancer syndrome (BRCA mutation) or hereditary nonpolyposis colorectal cancer (Lynch syndrome), and these women are at increased risk of developing ovarian cancer. Women with these conditions should be referred for formal genetic counseling to better assess their cancer risk, including their risk of ovarian cancer. If appropriate, these women may be offered additional testing for early detection of ovarian cancer. The use of transvaginal ultrasonography and tumor markers (such as cancer antigen 125), alone or in combination, for the early detection of ovarian cancer in average-risk women have not been proved to reduce mortality, and harms exist from invasive diagnostic testing (eg, surgery) resulting from false-positive test results. The patient and her obstetrician-gynecologist should maintain an appropriate level of suspicion when potentially relevant signs and symptoms of ovarian cancer are present.

Steady, relentless progress towards effective, safe screening for early detection of cancer of the ovary.

The quest for early detection of ovarian cancer (OC), in the hope of reducing mortality, began as soon as the correlation between stage and survival were documented >50 years ago. Research commenced in earnest in the 1980s when the CA 125 test became available1 and ultrasound technology was able to image the ovary2. The challenges were quickly recognised. Alongside acceptability, compliance and cost two issues needed addressing before large randomised trials with mortality as an end point could be justified. This article is protected by copyright. All rights reserved.

Ovarian cancer recurrence and early detection: may HE4 play a key role in this open challenge? A systematic review of literature.

Despite the improvement in overall survival for ovarian cancer (OC) patients, a fraction of patients with advanced-stage disease fails to respond to primary therapy and relapses in 70% of cases. For this reason, new predictive and monitoring tools are needed to identify OC recurrence and new biomarkers were studied, among which human epididymis 4 (HE4), primarily expressed in the reproductive and respiratory tracts, is one of the most promising, reporting a good sensitivity and specificity in detecting OC, overcoming the traditional role of carbohydrate antigen 125 (CA-125). In this review, we aim to discuss the latest evidence reported in the literature about the use of HE4 to monitor ovarian cancer treatment and to detect OC recurrence. We searched MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google Scholar; British Library) from January 1952 to June 2017. The search identified seven papers in line with eligibility criteria for this systematic review; all of them demonstrated a good performance of HE4 in OC recurrence. The challenge to anticipate the diagnosis of OC recurrence and to translate this early diagnosis of relapse in a survival and quality of life improvement is still open, and as reported in this review, HE4 may play a key role in this scenario. More studies are needed to validate and reinforce the role of HE4 in ovarian cancer recurrence and in its early detection.

Synergistic Tailoring of Electrostatic and Hydrophobic Interactions for Rapid and Specific Recognition of Lysophosphatidic Acid, an Early-Stage Ovarian Cancer Biomarker.

Early detection of ovarian cancer, the most lethal type of gynecologic cancer, can dramatically improve the efficacy of available treatment strategies. However, few screening tools exist for rapidly and effectively diagnosing ovarian cancer in early stages. Here, we present a facile "lock-key" strategy, based on rapid, specific detection of plasma lysophosphatidic acid (LPA, an early stage biomarker) with polydiacetylenes (PDAs)-based probe, for the early diagnosis of ovarian cancer. This strategy relies on specifically inserting LPA "key" into the PDAs "lock" through the synergistic electrostatic and hydrophobic interactions between them, leading to conformation transition of the PDA backbone with a concomitant blue-to-red color change. The detailed mechanism underlying the high selectivity of PDAs toward LPA is revealed by comprehensive theoretical calculation and experiments. Moreover, the level of LPA can be quantified in plasma samples from both mouse xenograft tumor models and patients with ovarian cancer. Impressively, this approach can be introduced into a portable point-of-care device to successfully distinguish the blood samples of patients with ovarian cancer from those of healthy people, with 100% accuracy. This work provides a valuable portable tool for early diagnosis of ovarian cancer and thus holds a great promise to dramatically improve the overall survival.

Systematic review: Tumor-associated antigen autoantibodies and ovarian cancer early detection.

Tumor-associated autoantibodies (AAbs), produced as an immune response to tumor-associated antigens (TAAs), are a novel pathway of early detection markers. We conducted a systematic review on AAbs and ovarian cancer to summarize the diagnostic performance of individual AAbs and AAb panels. A total of 29 studies including 85 AAbs were included; 27 of the studies were conducted in prevalent cases and cancer-free controls and 2 investigations included pre-diagnosis samples. The majority of studies were hypothesis-driven, evaluating AAbs to target TAAs; 10 studies used screening approaches such as serological expression cloning (SEREX) and nucleic acid-programmable protein arrays (NAPPA). The highest sensitivities for individual AAbs were reported for RhoGDI-AAbs (89.5%) and TUBA1C-AAbs (89%); however, specificity levels were relatively low (80% and 75%, respectively). High sensitivities at high specificities were reported for HOXA7-AAbs for detection of moderately differentiated ovarian tumors (66.7% sensitivity at 100% specificity) and IL8-AAbs in stage I-II ovarian cancer (65.5% sensitivity at 98% specificity). A panel of 11 AAbs (ICAM3, CTAG2, p53, STYXL1, PVR, POMC, NUDT11, TRIM39, UHMK1, KSR1, and NXF3) provided 45% sensitivity at 98% specificity for serous ovarian cancer, when at least 2 AAbs were above a threshold of 95% specificity. Twelve of the AAbs identified in this review were investigated in more than one study. Data on diagnostic discrimination by tumor histology and stage at diagnosis are sparse. Limited data suggest select AAb markers improve diagnostic discrimination when combined with markers such as CA125 and HE4. AAbs for ovarian cancer early detection is an emerging area, and large-scale, prospective investigations considering histology and stage are required for discovery and validation. However, data to date suggests panels of AAbs may eventually reach sufficient diagnostic discrimination to allow earlier detection of disease as a complement to existing markers and transvaginal ultrasound.

Tubal Cytology of the Fallopian Tube as a Promising Tool for Ovarian Cancer Early Detection.

Currently, it is widely accepted that the vast majority of ovarian high-grade serous carcinoma (HGSC) originate from the fallopian tube. However, due to the lack of markers or tools for the ovarian cancer identification, the early detection of HGSC remains challenging. Direct sampling of the fallopian tube can enhance sensitivity for detection of neoplastic cells when the tumor is not grossly visible. We developed a procedure to collect fallopian tube cells directly from freshly received surgical specimens, which has shown excellent correlation with histological findings. This approach lays a foundation for the future utility of minimally invasive laparoscopic screening in high-risk patient populations.

Tubal Cytology of the Fallopian Tube as a Promising Tool for Ovarian Cancer Early Detection

Tubal Cytology of the Fallopian Tube as a Promising Tool for Ovarian Cancer Early Detection