Sensor detection in gynaecological medicine

Thompson, Michael; Ahmadi, Soha; Davoudian, Katharina; Franier, Brian De La; Lotay, Navina; Bernardini, Marcus Q.

doi:10.1039/d2sd00090c

Cited by 6 publications

(8 citation statements)

References 230 publications

(500 reference statements)

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“…Around 90% of stage I patients have higher levels of the bioactive phospholipid lysophosphatidic acid (LPA) [4,5], a biomarker that can identify OC since average healthy levels of LPA are 1.2 µM, while OC can cause LPA concentrations of 1.3 to Biosensors 2024, 14, 287 2 of 15 50 µM [4,5]. An LPA screening test can potentially identify and monitor the progression of the disease since the level of LPA increases with OC development [3][4][5][6]. One approach for detecting LPA utilizes the gelsolin(1-3)-actin protein complex [6], which is separated upon LPA binding.…”

Section: Introductionmentioning

confidence: 99%

Design and Characterization of a Dual-Protein Strategy for an Early-Stage Assay of Ovarian Cancer Biomarker Lysophosphatidic Acid

Davoudian,

Spagnolo,

Lotay

et al. 2024

Biosensors

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The overall 5-year survival rate of ovarian cancer (OC) is generally low as the disease is often diagnosed at an advanced stage of progression. To save lives, OC must be identified in its early stages when treatment is most effective. Early-stage OC causes the upregulation of lysophosphatidic acid (LPA), making the molecule a promising biomarker for early-stage detection. An LPA assay can additionally stage the disease since LPA levels increase with OC progression. This work presents two methods that demonstrate the prospective application for detecting LPA: the electromagnetic piezoelectric acoustic sensor (EMPAS) and a chemiluminescence-based iron oxide nanoparticle (IONP) approach. Both methods incorporate the protein complex gelsolin–actin, which enables testing for detection of the biomarker as the binding of LPA to the complex results in the separation of gelsolin from actin. The EMPAS was characterized with contact angle goniometry and atomic force microscopy, while gelsolin–actin-functionalized IONPs were characterized with transmission electron microscopy and Fourier transform infrared spectroscopy. In addition to characterization, LPA detection was demonstrated as a proof-of-concept in Milli-Q water, buffer, or human serum, highlighting various LPA assays that can be developed for the early-stage detection of OC.

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Section: Introductionmentioning

confidence: 99%

Design and Characterization of a Dual-Protein Strategy for an Early-Stage Assay of Ovarian Cancer Biomarker Lysophosphatidic Acid

Davoudian,

Spagnolo,

Lotay

et al. 2024

Biosensors

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“…About 75% of OC patients are diagnosed very late, in stages III or IV [ 8 ], which significantly reduces the five-year survival rate, from above 90% in stage I to around 20–30% in stage IV. Epithelial OC, the most common OC subgroup, has the lowest survival rate [ 8 , 9 , 10 ]. Current OC diagnostic tests are limited by a substantial risk of false negatives, as well as false positives [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Cancer antigen 125 (CA-125) is the only OC blood serum biomarker that can be clinically tested, with a sensitivity of 75–82% and specificity of 67–76% [ 15 , 16 ]. As CA-125 can also be present in benign conditions and other cancers and is only increased in about 50% of early stage OC patients, this inconclusive blood test for OC must be combined with the expensive and time-consuming imaging techniques [ 7 , 10 , 15 ]. Blood levels of CA-125 increase as OC advances and it is present in about 92% of advanced-stage patients, making it more useful for monitoring disease progression during treatment [ 10 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, an LPA assay can be useful for monitoring OC as other works reported that LPA levels increase with the advancement of OC. This suggests that LPA detection in plasma or serum can identify the stage of the disease [ 10 , 15 , 17 ], which is crucial for stratifying patients and developing personalised treatments appropriate to the disease state. While the average healthy LPA concentration is 1.2 µM, levels can surge from 1.3 to 50 µM depending on the OC stage [ 17 , 23 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Coupled Electrostatic and Hydrophobic Destabilisation of the Gelsolin-Actin Complex Enables Facile Detection of Ovarian Cancer Biomarker Lysophosphatidic Acid

Davoudian,

Bhattacharya,

Thompson

et al. 2023

Biomolecules

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Lysophosphatidic acid (LPA) is a promising biomarker candidate to screen for ovarian cancer (OC) and potentially stratify and treat patients according to disease stage. LPA is known to target the actin-binding protein gelsolin which is a key regulator of actin filament assembly. Previous studies have shown that the phosphate headgroup of LPA alone is inadequate to bind to the short chain of amino acids in gelsolin known as the PIP2-binding domain. Thus, the molecular-level detail of the mechanism of LPA binding is poorly understood. Here, we model LPA binding to the PIP2-binding domain of gelsolin in the gelsolin-actin complex through extensive ten-microsecond atomistic molecular dynamics (MD) simulations. We predict that LPA binding causes a local conformational rearrangement due to LPA interactions with both gelsolin and actin residues. These conformational changes are a result of the amphipathic nature of LPA, where the anionic phosphate, polar glycerol and ester groups, and lipophilic aliphatic tail mediate LPA binding via charged electrostatic, hydrogen bonding, and van der Waals interactions. The negatively-charged LPA headgroup binds to the PIP2-binding domain of gelsolin-actin while its hydrophobic tail is inserted into actin, creating a strong LPA-insertion pocket that weakens the gelsolin–actin interface. The computed structure, dynamics, and energetics of the ternary gelsolin–LPA–actin complex confirms that a quantitative OC assay is possible based on LPA-triggered actin release from the gelsolin-actin complex.

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“…For this reason, the detection of related biomarkers is crucial for early detection, differential diagnosis, treatment selection, and monitoring of treatment response. Integrating biomarkers into clinical practice enhances the precision and personalized management of ovarian cancer, ultimately improving patient outcome and survival rate [22,23]. During the last few decades, a large number of biomarkers have been evaluated for their ability to detect epithelial ovarian cancer at an early stage [23].…”

Section: Introductionmentioning

confidence: 99%

Cancer Marker Immunosensing through Surface-Enhanced Photoluminescence on Nanostructured Silver Substrates

Geka,

Kanioura,

Kochylas

et al. 2023

Nanomaterials

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Nanostructured noble metal surfaces enhance the photoluminescence emitted by fluorescent molecules, permitting the development of highly sensitive fluorescence immunoassays. To this end, surfaces with silicon nanowires decorated with silver nanoparticles in the form of dendrites or aggregates were evaluated as substrates for the immunochemical detection of two ovarian cancer indicators, carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4). The substrates were prepared by metal-enhanced chemical etching of silicon wafers to create, in one step, silicon nanowires and silver nanoparticles on top of them. For both analytes, non-competitive immunoassays were developed using pairs of highly specific monoclonal antibodies, one for analyte capture on the substrate and the other for detection. In order to facilitate the identification of the immunocomplexes through a reaction with streptavidin labeled with Rhodamine Red-X, the detection antibodies were biotinylated. An in-house-developed optical set-up was used for photoluminescence signal measurements after assay completion. The detection limits achieved were 2.5 U/mL and 3.12 pM for CA125 and HE4, respectively, with linear dynamic ranges extending up to 500 U/mL for CA125 and up to 500 pM for HE4, covering the concentration ranges of both healthy and ovarian cancer patients. Thus, the proposed method could be implemented for the early diagnosis and/or prognosis and monitoring of ovarian cancer.

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Sensor detection in gynaecological medicine

Abstract: Gynecological medicine involves the diagnoses and treatment of illnesses and issues involving female reproductive organs. This review is focused on female cancers of their reproductive organs including ovarian cancer, cervical...

Cited by 6 publications

References 230 publications

Design and Characterization of a Dual-Protein Strategy for an Early-Stage Assay of Ovarian Cancer Biomarker Lysophosphatidic Acid

Design and Characterization of a Dual-Protein Strategy for an Early-Stage Assay of Ovarian Cancer Biomarker Lysophosphatidic Acid

Coupled Electrostatic and Hydrophobic Destabilisation of the Gelsolin-Actin Complex Enables Facile Detection of Ovarian Cancer Biomarker Lysophosphatidic Acid

Cancer Marker Immunosensing through Surface-Enhanced Photoluminescence on Nanostructured Silver Substrates

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