Article

Detection of Prostate Cancer using Voltammetric Electronic Tongue

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Abstract

A simple method based on multivariate analysis of data from urine using an electronic voltammetric tongue is used to detect patients with prostate cancer. A sensitivity of 91% and a specificity of 73% was obtained to distinguish urine from cancer patients and urine from non cancer patients.

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... integrate a system of non-specific sensors whose response can be analysed with a pattern recognition algorithm or multivariate analysis (Winquist, 2008), presenting remarkable capabilities for classification and quantification of physicochemical parameters. Application examples range from quality assessment in food (Cetó et al., 2016;Peris and Escuder-Gilabert, 2016;Tan and Xu, 2020) water (Cetó et al., 2016), environmental studies (Cetó and Valle, 2022) to pharmaceutics (Wasilewski et al., 2019) and biomedicine (Belugina et al., 2021;Braz et al., 2022;Lvova et al., 2009;Pascual et al., 2016;Solovieva et al., 2019) among others. ...
... A sensitivity and specificity >90% for the discrimination of PCa and healthy controls was obtained by Solovieva et al. with a potentiometric e-tongue in a set of 89 urines (Solovieva et al., 2019). VET has shown also a high sensitivity (91%) and specificity (73%) for the diagnosis of PCa in a set of 114 urines of patients with PCa and healthy controls, and are also promising for the application of this tool in the BC field (Pascual et al., 2016). Nevertheless, the context in the study of PCa and BC are different. ...
... Also deserves to be mentioned the fact that the set up here presented enables the study of this reduced volume without any dilution, which improves the results of this technique. Finally, the Ni working electrode has been here demonstrated to be important in the discriminant model, which was not used previously in the study of PCa by VET (Pascual et al., 2016). ...
Article
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Bladder cancer (BC) is the sixth leading cause of death by cancer. Depending on the invasiveness of tumours, BC patients will undergo surgery and surveillance lifelong, owing the high rate of recurrence and progression. In this context, the development of strategies to support non-invasive BC diagnosis is focusing attention. Voltammetric electronic tongue (VET) has been demonstrated to be of use in the analysis of biofluids. Here we present the implementation of a VET to study 207 urines to discriminate BC and non-BC for diagnosis and surveillance to detect recurrences. Special attention has been paid to the experimental setup to improve reproducibility in the measurements. PLSDA analysis together with variable selection provided a model with high sensitivity, specificity and area under the ROC curve AUC (0.844, 0.882 and 0.917 respectively). These results pave the way for the development of non-invasive low-cost and easy-to-use strategies to support BC diagnosis and follow-up.
... This system has been used to measure different biological samples (urine, exudates collected from cutaneous ulcers) with promising results. VA can detect levels of uremic toxins 5 , urinary creatinine and the severity of renal insufficiency; it also allows to discriminate urine of healthy subjects from urine of patients with benign or malignant bladder 6 and prostate tumors 7 . Furthermore, it has been confirmed that VA is a powerful technique to diagnose UTI 8 . ...
... It is likely that retesting it in a pure and larger population of spontaneous effusions would disclose better clinimetric properties. Secondly, we performed the voltammetric analysis according to the methods previously developed for the diagnosis of skin and bladder infections [5][6][7][8][9] . However, this might not be the best option for identifying a neoplastic pleural effusion. ...
Article
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Pleural effusion is very common, but an etiologic diagnosis is often difficult. We used three unconventional diagnostic techniques (voltammetric analysis, protein electrophoresis and pH measurement) performed on pleural effusion to do a preliminary distinction between a neoplastic and a non-neoplastic origin. Pleural fluid samples were collected through thoracentesis, thoracoscopy, or post-surgery pleural drainage of 116 patients admitted to acute care wards. Samples were analyzed with the three unconventional techniques: voltammetric analysis using the BIONOTE system, capillary electrophoresis and pH measurement using a potentiometric method. The BIONOTE system is an innovative system that performs a cyclic voltammetric analysis of a biological liquid sample. The final output of the electrochemical analysis is an electrical pattern that represents a fingerprint of the analyzed sample and each sample has a different fingerprint. Data from the three unconventional diagnostic techniques were analyzed using partial least squares discriminant analysis to discriminate neoplastic from non-neoplastic effusions; we also evaluated sensitivity, specificity and percentage of correct classification. The mean age was 68 years (SD: 12); 78 (67.24%) participants were men. Results obtained from all the unconventional techniques employed showed that neoplastic and non-neoplastic pleural effusions were correctly classified in 80.2% of cases, with a sensitivity of 77% and specificity of 83%. The combined use of voltammetric analysis, protein electrophoresis and pH measurement of pleural fluid can easily and quickly distinguish a neoplastic from a non-neoplastic pleural effusion with reliable accuracy and represents an innovative diagnostic approach. In fact, this protocol can be executed in just few minutes directly in the patient's bed and it holds great promise to improve the prognosis and therapeutic chances.
... In another study, PLS-DA was employed for the classication of urine samples from 22 prostate cancer and 15 non-cancer patients using the multivariate electrochemical proles measured on a 7-electrode electronic voltammetric tongue, achieving 91% sensitivity and 73% specicity. 116 The aforementioned examples thus illustrate the ability of PLS algorithms to construct accurate classication or regression models from multivariate datasets, which portray distinct linear trends or separations. ...
Article
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Speedy, point-of-need detection and monitoring of small-molecule metabolites are vital across diverse applications ranging from biomedicine to agri-food and environmental surveillance. Nanomaterial-based sensor (nanosensor) platforms are rapidly emerging as excellent candidates for versatile and ultrasensitive detection owing to their highly configurable optical, electrical and electrochemical properties, fast readout, as well as portability and ease of use. To translate nanosensor technologies for real-world applications, key challenges to overcome include ultralow analyte concentration down to ppb or nM levels, complex sample matrices with numerous interfering species, difficulty in differentiating isomers and structural analogues, as well as complex, multidimensional datasets of high sample variability. In this Perspective, we focus on contemporary and emerging strategies to address the aforementioned challenges and enhance nanosensor detection performance in terms of sensitivity, selectivity and multiplexing capability. We outline 3 main concepts: (1) customization of designer nanosensor platform configurations via chemical-and physical-based modification strategies, (2) development of hybrid techniques including multimodal and hyphenated techniques, and (3) synergistic use of machine learning such as clustering, classification and regression algorithms for data exploration and predictions. These concepts can be further integrated as multifaceted strategies to further boost nanosensor performances. Finally, we present a critical outlook that explores future opportunities toward the design of next-generation nanosensor platforms for rapid, point-of-need detection of various small-molecule metabolites.
... Comparando los resultados obtenidos en este proyecto (los del modelo clasificador ensemble basado en SVM sin variables adicionales) con los resultados obtenidos por Loras et al. (2016) [7], se ha obtenido una menor sensibilidad (76.4% contra 86.4%) y especificidad (77.5% contra 80.9%), no batiendo los resultados obtenidos mediante espectroscopia de RMN. La ventaja de la lengua electrónica voltamétrica, pese a su menor poder de clasificación, es su capacidad de medición in situ e instantánea, de forma económica y sencilla (sin necesidad de personal altamente cualificado), características que no comparte con la espectroscopia de RMN, por lo que puede ser utilizada como método de cribado o screening, para posteriormente utilizar otras técnicas más sofisticadas, más invasivas o con mayor sensibilidad y especificidad. ...
Thesis
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The bladder cancer early detection is nowadays done through urine analysis of metabolites. This technique offers high specificity (>90%) but with moderate sensibility (<50%), and presents a temporal and economic cost related with the need of laboratory analysis. A candidate for replacing this technique is the use of an electronic tongue, which has given positive results for the prostate cancer early detection application. The electronic tongue would allow obtaining immediate results with practically any variable cost. In this project is developed and combined different classifying algorithms based on the measurements realized at La Fe Polytechnic Hospital through FraPlusMini equipment, an electronic tongue developed by IDM, at the same time that it is performed an analysis to improve the device for the application. Focused in these objectives multivariate analysis, data mining and neural networks are combined.
... Although urine commonly contains a mixture of low molecular mass and even volatile compounds, which can be detected by the senses (interestingly, also by using trained dogs) [82] or using a low-cost array of different electrodes (Ir, Rh, Pt, Au, Ag, Co and Cu, d = 2 mm)-so-called voltammetric electronic tongue (sensitivity 91% and a specificity 73% to detect PCa individuals) [83], the specific detection of a PCa biomarker is usually achieved by using a bioreceptive element. Citrate is an important part of a prostatic fluid, being produced by prostate cells with its level being affected directly by intracellular Zn concentration. ...
Article
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The review initially provides a short introduction to prostate cancer (PCa) incidence, mortality, and diagnostics. Next, the need for novel biomarkers for PCa diagnostics is briefly discussed. The core of the review provides details about PCa aetiology, alternative biomarkers available for PCa diagnostics besides prostate specific antigen and their biosensing. In particular, low molecular mass biomolecules (ions and metabolites) and high molecular mass biomolecules (proteins, RNA, DNA, glycoproteins, enzymes) are discussed, along with clinical performance parameters.
... Compared to the human gustatory system, the e-tongue is able to detect compounds far below the human threshold in complex matrices (Riul et al., 2003c;Riul et al., 2010;Jiang et al., 2018). In addition, to taste analyses (Riul et al., 2002(Riul et al., , 2003aManzoli et al., 2014;Daikuzono et al., 2015), the e-tongue also enables the analysis of inedible media and unpleasant formulations (Riul et al., 2010;Kirsanov et al., 2019), such as biological samples (Ciosek et al., 2008;Heras et al., 2010;Ha et al., 2015;Pascual et al., 2016), pollutants (Mimendia et al., 2010;Campos et al., 2012;Magro et al., 2019;Tazi et al., 2020), hazardous and toxic analytes (Kirsanov et al., 2013;Agir and Kundu, 2016;Cruz et al., 2018;Shimizu et al., 2019), pharmaceutics (Woertz et al., 2011a, b;Choi et al., 2014;Wesoły et al., 2017;Krieser et al., 2020;Facure et al., 2020), etc. To attend the desired characteristics and a high performance, the architecture of the sensing units, namely the materials employed in the composition of the e-tongue, must be accurately chosen (Vlasov et al., 2008;Riul et al., 2010;Ha et al., 2015). ...
Chapter
In this book chapter we review recent advances on the use of electrospun and solution-blow spun nanofibers, which display remarkable features as high surface area to volume ratio, high porosity, mechanical flexibility and possibility of functionalization, in the design of chemoresistive, electrochemical, opto-chemical and electronic-tongue sensors. Emphasizes is given on the fabrication of nanofibers of varied size, shape as well as with distinct surface and bulk functionalization with active compounds to interact with analytes ranging from heavy metals, food contaminants, microorganism, volatile organic compounds, among others. Finally, future trends for nanofibers fabrication and application in sensors are also discussed.
... A voltammetric MSS comprising seven working electrodes (Ir, Rh, Pt, Au, Ag, Co, and Cu) versus saturated calomel reference electrodes was applied to detect patients with prostate cancer (PCa) [64]. The sample set comprised 114 samples: 71 samples from the patients with PCa before surgical treatment and 43 controls (26 from patients who underwent the surgery and 17 from individuals with benign prostatic hyperplasia). ...
Article
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“Electronic tongues”, “taste sensors”, and similar devices (further named as “multisensor systems”, or MSS) have been studied and applied mostly for the analysis of edible analytes. This is not surprising, since the MSS development was sometimes inspired by the mainstream idea that they could substitute human gustatory tests. However, the basic principle behind multisensor systems—a combination of an array of cross-sensitive chemical sensors for liquid analysis and a machine learning engine for multivariate data processing—does not imply any limitations on the application of such systems for the analysis of inedible media. This review deals with the numerous MSS applications for the analysis of inedible analytes, among other things, for agricultural and medical purposes.
... Voltammetry was also employed as a platform for recognition in medicine. The report [22] was exploring the potential of the voltammetric multisensor system in distinguishing urine samples from the patients with PCa and control group. Using 114 urine samples (71 with PCa and 43 control) and partial least squaresdiscriminant analysis the authors achieved sensitivity and specificity of 91% and 73%, correspondingly, however only one classification technique was employed (PLS-DA). ...
Article
We report a simple potentiometric multisensor system for distinguishing the urine samples from the patients with diagnosed prostate cancer and from healthy control group. The sensors of the system are sensitive towards variety of cationic and anionic species in urine, as well as to the presence of RedOx pairs. The response of the system represents a complex chemical fingerprint of urine sample that can be related with patient status through multivariate modelling. 89 urine samples were studied (43 from cancer patients confirmed by prostatic puncture biopsy and 46 from healthy control group) and variety of multivariate classification techniques was applied to the potentiometric data. The best results were obtained with logistic regression model yielding 100% sensitivity and 93% specificity in the independent test set of samples.
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The diagnosis of cancer and other diseases using data from non-specific sensors – such as the electronic tongues (e-tongues) - is challenging owing to the lack of selectivity, in addition to the variability of biological samples. In this study, we demonstrate that impedance data obtained with an e-tongue in saliva samples can be used to diagnose cancer in the mouth. Data taken with a single-response microfluidic e-tongue applied to the saliva of 27 individuals were treated with multidimensional projection techniques and non-supervised and supervised machine learning algorithms. The distinction between healthy individuals and patients with cancer on the floor of mouth or oral cavity could only be made with supervised learning. Accuracy above 80% was obtained for the binary classification (YES or NO for cancer) using a support vector machine (SVM) with radial basis function kernel and random forests. In the classification considering the type of cancer, the accuracy dropped to ca. 70%. The accuracy tended to increase when clinical information such as alcohol consumption was used in conjunction with the e-tongue data. With the random forest algorithm, the rules to explain the diagnosis could be identified using the concept of multidimensional calibration space. Since the training of the machine learning algorithms is believed to be more efficient when the data of a larger number of patients are employed, the approach presented here is promising for computer-assisted diagnosis.
Chapter
The main reason to resort to electronic tongues arises in situations where the use of a human panel is not possible, such as in the continuous monitoring of industrial processes, analysis of unpleasant or poisonous/hazardous samples (drugs, virus, bacteria, pollutants), and for economical limitations. This chapter describes recent advances with special emphasis on microfluidic platforms based on polymers and paper, new designs, and new sensing and biosensing applications. The use of electroactive species to provide high specificity in pharmaceuticals enabled the e‐tongue application to detect atenolol and propranolol, insulin, diclofenac, and amino acids. Bio e‐tongues have been used in water analysis; to discriminate varieties of grapes through phenolic and sugar content; to detect phytic acid; for the diagnosis of Chagas and Leishmaniasis diseases; and to detect catechol, glucose, and triglycerides. Microfluidic systems appeared after C.M. Daikuzono et al. proved the successful usage of the first microfluidic e‐tongue design.
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Voltammetric electronic tongue (VE-tongue) is a promising technology for advanced sensing and measurement applications. The review examines the measurement principles, working parameters and configurations of different types of voltammetric electronic tongues (VE-tongue): the VE-tongue based on bare electrodes, modified electrodes and biosensors. The working parameters of these VE-tongues (electrode cleaning method, pulsed voltammetry and pre-processing of responses data) are described, and the development of VE-tongue based on miniaturized sensors arrays and automatic flow techniques is also presented. The applications of foodstuff analysis commented include recognition of basic tastes substances, tracing origins/samples recognition, process monitoring, and quality investigation. Finally, the unsolved problems and significant efforts of VE-tongues are depicted.
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This review discusses basic principles and applications of voltammetric electronic tongues. It is introduced by a description of the concept of electronic tongues or taste sensors followed by a general overview of electrochemical measurement principles that have been used for electronic tongues. A special emphasis is given on measurement principles for voltammetric electronic tongues, also including pulse voltammetry and variable reduction. Applications of voltammetric electronic tongue are described, such as in the food industry, environmental analysis, paper and pulp industry, household appliances and agriculture. Future developments of the concept, such as self polishing or miniaturized devices are also described. Finally, a continuous measurement system for chemical oxygen demand (COD), which has been commercialized, is depicted.
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This minireview describes the main developments of electronic tongues (e-tongues) and taste sensors in recent years, with a summary of the principles of detection and materials used in the sensing units. E-tongues are sensor arrays capable of distinguishing very similar liquids employing the concept of global selectivity, where the difference in the electrical response of different materials serves as a fingerprint for the analysed sample. They have been widely used for the analysis of wines, fruit juices, coffee, milk and beverages, in addition to the detection of trace amounts of impurities or pollutants in waters. Among the various principles of detection, electrochemical measurements and impedance spectroscopy are the most prominent. With regard to the materials for the sensing units, in most cases use is made of ultrathin films produced in a layer-by-layer fashion to yield higher sensitivity with the advantage of control of the film molecular architecture. The concept of e-tongues has been extended to biosensing by using sensing units capable of molecular recognition, as in films with immobilized antigens or enzymes with specific recognition for clinical diagnosis. Because the identification of samples is basically a classification task, there has been a trend to use artificial intelligence and information visualization methods to enhance the performance of e-tongues.
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Serum prostate specific antigen (PSA) levels were measured in 139 patients with benign prostatic hyperplasia (BPH) and in 88 patients with prostate cancer who were managed by deferred treatment. Acute urinary retention and large prostate glands tended to be associated with high PSA levels, but at levels greater than 10 ng/ml there was a significant risk of carcinoma being found on subsequent histological examination. The risk of progression of untreated prostate cancer was associated with levels of PSA greater than 20 ng/ml and with a high rate of change of PSA level. The value of measuring PSA in these patients is discussed.
Article
The purpose of this study was to examine the diagnostic efficiency of prostate-specific antigen (PSA) and digital rectal examination (DRE) testing when using either 4.0 ng/ml or an age-specific reference range (ASRR) as an abnormal cutoff PSA value. Between 1992-1995, 116,073 men, aged 40-79 years, were screened during Prostate Cancer Awareness Week. When using a 4.0-ng/ml cutoff PSA value, 22,014 had either an abnormal PSA, an abnormal DRE, or both. When using an ASRR cutoff PSA value, 17,561 had either an abnormal PSA, an abnormal DRE, or both. The positive predictive value (PPV), sensitivity, and specificity of PSA, DRE, and combined PSA and DRE tests were evaluated. When using a 4.0-ng/ml cutoff PSA value, the PPVs of abnormal PSA alone, abnormal DRE alone, and combined abnormal PSA and DRE tests were 27.7%, 17.7%, and 56.0%, respectively. Sensitivities were 34.9%, 27.1%, and 38.0%, respectively. Specificities were 63.1%, 49.0%, and 87.9%, respectively. When using an ASRR cutoff PSA value, the PPVs of each category were 31.8%, 20.8%, and 63.7%, respectively. Sensitivities were 27.1%, 41.0%, and 31.8%, respectively. Specificities were 75.0%, 32.8%, and 92.2%, respectively. The PPVs of the PSA test were higher than those of the DRE. The PPVs of combined tests were highest when using either a 4.0-ng/ml cutoff PSA value or an ASRR cutoff PSA value (all P < 0.001). When using an ASRR, the PPVs of PSA, DRE, and combined tests were higher than those when using a 4.0-ng/ml without statistical significance (all P > 0.05). Sensitivity of PSA when using an ASRR was lower than when using 4.0 ng/ml. Significantly higher PPVs indicated that utilizing both a PSA test and a DRE is most effective in screening for the early detection of prostate cancer. Although higher PPVs when using an ASRR cutoff PSA value suggested fewer unnecessary biopsies, lower sensitivities resulted in fewer cancers detected. Thus, we recommend that the combination of a PSA test with a cutoff value of 4.0 ng/ml and a DRE should continue to be utilized in the screening programs.
Article
To retrospectively investigate the use of percent free prostate-specific antigen (PSA) compared with total PSA in serum as predictor of prostate cancer in men selected randomly from the general population who underwent biopsy on the basis of abnormal findings on digital rectal examination (DRE) or transrectal ultrasound (TRUS) and/or serum PSA levels greater than 10 ng/mL. A single intervention, population-based screening study was undertaken in 1988 and 1989. Of the 2400 men aged 55 to 70 years invited to participate, 1782 men responded and were examined with DRE, TRUS, and PSA testing (Tandem-Hybritech). In 1995, frozen serum samples from 1748 men were analyzed for percent free PSA (Prostatus, Wallac OY). Five-year follow-up data on new cancers in the screened population were obtained from the Swedish Cancer Registry (SCR). Of the 1748 men, 367 underwent TRUS-guided biopsies because of abnormal findings on either DRE or TRUS or serum PSA levels of greater than 10 ng/mL. This resulted in the diagnosis of 64 cases of prostate cancer (3.7%). PSA levels of 3.0 ng/mL or greater were found in 55 (86%) of 64 cancer cases and in 399 (24%) of the 1684 benign cases. Among the 1294 men with PSA less than 3.0 ng/mL, 9 prostate cancers were diagnosed (14% of all prostate cancers). All 9 patients with cancer and with PSA less than 3.0 ng/mL had a percent free PSA of 18% or less. In the group of 1109 patients with PSA less than 3.0 ng/mL and a percent free PSA greater than 18%, 159 biopsies were performed because of abnormal DRE or TRUS. However, no prostate cancer was diagnosed in this category of patients. Five years after the screening intervention, 7 more cases of prostate cancer were clinically diagnosed in the screened population according to the SCR. The combination of PSA levels less than 3.0 ng/mL and percent free PSA greater than 18% defines a large part of the population at a very low risk of cancer of the prostate both at the time of screening and during the following 5 years. Men in this group may be spared DRE, and longer screening intervals may be considered. However, the risk of having prostate cancer is not negligible in men with PSA less than 3.0 ng/mL and percent free PSA of 18% or less. The results of this study indicate that biopsy should be recommended to men fulfilling these criteria, although these results should be confirmed in larger prospective studies because of the limited number of patients with prostate cancer in the present series.
Article
At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, however, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) play an important role as regulatory mediators in signaling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress and reestablish "redox homeostasis." Higher organisms, however, have evolved the use of NO and ROS also as signaling molecules for other physiological functions. These include regulation of vascular tone, monitoring of oxygen tension in the control of ventilation and erythropoietin production, and signal transduction from membrane receptors in various physiological processes. NO and ROS are typically generated in these cases by tightly regulated enzymes such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. In a given signaling protein, oxidative attack induces either a loss of function, a gain of function, or a switch to a different function. Excessive amounts of ROS may arise either from excessive stimulation of NAD(P)H oxidases or from less well-regulated sources such as the mitochondrial electron-transport chain. In mitochondria, ROS are generated as undesirable side products of the oxidative energy metabolism. An excessive and/or sustained increase in ROS production has been implicated in the pathogenesis of cancer, diabetes mellitus, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and other diseases. In addition, free radicals have been implicated in the mechanism of senescence. That the process of aging may result, at least in part, from radical-mediated oxidative damage was proposed more than 40 years ago by Harman (J Gerontol 11: 298-300, 1956). There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.
  • L C Costello
  • R B Franklin
  • J L Griffin
  • J P Shockcor
L. C. Costello and R. B. Franklin, Mol. Cancer, 2006, 5, 17. 11 J. L. Griffin and J. P. Shockcor, Nat. Rev. Cancer, 2004, 4, 551–561. 12 C. Abate‐Shen and M. M. Shen, Nature, 2009, 457, 799– 800.
  • Di Natale
  • A D Amico
  • Talanta M Gutiérrez
  • S Alegret
  • M Del Valle
  • R Traverso
  • M Ricciarelli
  • B Nitti
  • A L Marengo
  • M A Furfaro
  • U M Pronzato
  • C Marinari
  • Domenicotti
Di Natale and A. D'Amico, Talanta, 2009, 77, 1097–104. 27 M. Gutiérrez, S. Alegret and M. del Valle, Biosens. Bioelectron., 2007, 22, 2171–2178. 28 N. Traverso, R. Ricciarelli, M. Nitti, B. Marengo, A. L. Furfaro, M. A. Pronzato, U. M. Marinari and C. Domenicotti, Oxid. Med. Cell. Longev., 2013, 2013. 29 W. Dröge, Physiol Rev, 2002, 82, 47–95. 30 B. J. Trock, Urol. Oncol., 2011, 29, 572–581. 31 I. Campos, M. Alcañiz, R. Masot, J. Soto, R. Martínez‐ Máñez, J. L. Vivancos and L. Gil, Sensors Actuators, B Chem., 2012, 161, 556–563.
  • A Alexander
  • J R Berger
  • J T Shuster
  • Wei
Alexander, A. Berger, J. R. Shuster and J. T. Wei, Nature, 2009, 457, 910-914.
  • M Truong
  • B Yang
  • D Jarrard
M. Truong, B. Yang and D. Jarrard, J. Urol., 2013, 189, 422– 429. 24 F. Winquist, Microchim. Acta, 2008, 163, 3–10. 25 A. Riul, C. a R. Dantas, C. M. Miyazaki and O. N. Oliveira, Analyst, 2010, 135, 2481–2495. 26 L. Lvova, E. Martinelli, F. Dini, A. Bergamini, R. Paolesse, C.
  • U Törnblom
  • J Norming
  • C Adolfsson
  • P.-A Becker
  • H Abrahamsson
  • O Lilja
  • Gustafsson
Törnblom, U. Norming, J. Adolfsson, C. Becker, P.-A. Abrahamsson, H. Lilja and O. Gustafsson, Urology, 1999, 53, 945-950.
  • J L Zaragozá
  • G Ruiz-Cerdá
  • S Quintás
  • A M Gil
  • Z Costero
  • J.-L León
  • R Vivancos
  • Martínezmáñez
. Zaragozá, J. L. Ruiz-Cerdá, G. Quintás, S. Gil, A. M. Costero, Z. León, J.-L. Vivancos and R. MartínezMáñez, Analyst, 2014, 139, 3875-3878.
  • D Siegel
  • A Naishadham
  • Jemal
Siegel, D. Naishadham and A. Jemal, CA-Cancer J. Clin., 2013, 63, 11-30.
  • M M Abate-Shen
  • Shen
Abate-Shen and M. M. Shen, Nature, 2009, 457, 799-800.
  • J.-N Cornu
  • G Cancel-Tassin
  • V Ondet
  • C Girardet
  • O Cussenot
J.-N. Cornu, G. Cancel-Tassin, V. Ondet, C. Girardet and O. Cussenot, Eur. Urol., 2011, 59, 197-201.
  • A J Kobus
  • E Wright
  • A Weiland
  • T W J Heerschap
  • Scheenen
Kobus, A. J. Wright, E. Weiland, A. Heerschap and T. W. J. Scheenen, Magn. Reson. Med., 2015, 73, 1-12.
  • W J Catalona
  • A V D'amico
  • W F Fitzgibbons
  • O Kosoko-Lasaki
  • S W Leslie
  • H T Lynch
  • J W Moul
  • M S Rendell
  • P C Walsh
W. J. Catalona, A. V. D'Amico, W. F. Fitzgibbons, O. Kosoko-Lasaki, S. W. Leslie, H. T. Lynch, J. W. Moul, M. S. Rendell and P. C. Walsh, Ann. Intern. Med., 2012, 157, 137.
  • B Truong
  • D Yang
  • Jarrard
Truong, B. Yang and D. Jarrard, J. Urol., 2013, 189, 422-429.
  • A Moyer
A. Moyer, Ann. Intern. Med., 2012, 157, 120.
  • C A R Riul
  • C M Dantas
  • O N Miyazaki
  • Oliveira
Riul, C. a. R. Dantas, C. M. Miyazaki and O. N. Oliveira, Analyst, 2010, 135, 2481-2495.
  • T G Armitage
  • E H Cooper
  • D W W Newling
  • M R G Robinson
  • I Appleyard
T. G. Armitage, E. H. Cooper, D. W. W. Newling, M. R. G. Robinson and I. Appleyard, Br. J. Urol., 1988, 62, 584-589.
  • L M Sreekumar
  • T M Poisson
  • A P Rajendiran
  • Q Khan
  • J Cao
  • B Yu
  • R Laxman
  • R J Mehra
  • Y Lonigro
  • M K Li
  • A Nyati
  • S Ahsan
  • B Kalyana-Sundaram
  • X Han
  • Cao
Sreekumar, L. M. Poisson, T. M. Rajendiran, A. P. Khan, Q. Cao, J. Yu, B. Laxman, R. Mehra, R. J. Lonigro, Y. Li, M. K. Nyati, A. Ahsan, S. Kalyana-sundaram, B. Han, X. Cao, J. Byun, G. S. Omenn, D. Ghosh, S. Pennathur, D. C. Alexander, A. Berger, J. R. Shuster and J. T. Wei, Nature, 2009, 457, 910-914.
  • E Lvova
  • F Martinelli
  • A Dini
  • R Bergamini
  • C Di Paolesse
  • A D Natale
  • Amico
Lvova, E. Martinelli, F. Dini, A. Bergamini, R. Paolesse, C. Di Natale and A. D'Amico, Talanta, 2009, 77, 10971104.
  • N Traverso
  • R Ricciarelli
  • M Nitti
  • B Marengo
  • A L Furfaro
  • M A Pronzato
  • U M Marinari
  • C Domenicotti
28 N. Traverso, R. Ricciarelli, M. Nitti, B. Marengo, A. L. Furfaro, M. A. Pronzato, U. M. Marinari and C. Domenicotti, Oxid. Med. Cell. Longevity, 2013, 2013, 972913. 29 W. Dröge, Physiol. Rev., 2002, 82, 47-95.
  • M Campos
  • R Alcañiz
  • J Masot
  • R Soto
  • J L Martínezmáñez
  • L Vivancos
  • Gil
Campos, M. Alcañiz, R. Masot, J. Soto, R. MartínezMáñez, J. L. Vivancos and L. Gil, Sens. Actuators, B, 2012, 161, 556-563.
  • R R Drake
  • K Y White
  • T W Fuller
  • E Igwe
  • M A Clements
  • J O Nyalwidhe
  • R W Given
  • R S Lance
  • O J Semmes
R. R. Drake, K. Y. White, T. W. Fuller, E. Igwe, M. A. Clements, J. O. Nyalwidhe, R. W. Given, R. S. Lance and O. J. Semmes, J. Proteomics, 2009, 72, 907-917.
  • L L Cheng
  • M A Burns
  • J L Taylor
  • W He
  • E F Halpern
  • W S Mcdougal
  • C L Wu
L. L. Cheng, M. A. Burns, J. L. Taylor, W. He, E. F. Halpern, W. S. McDougal and C. L. Wu, Cancer Res., 2005, 65, 3030-3034.
  • L Griffin
  • J P Shockcor
L. Griffin and J. P. Shockcor, Nat. Rev. Cancer, 2004, 4, 551–561.
  • S Gutiérrez
  • M Alegret
  • Valle
Gutiérrez, S. Alegret and M. del Valle, Biosens. Bioelectron., 2007, 22, 2171-2178.
  • E.-M Spur
  • E A Decelle
  • L L Cheng
E.-M. Spur, E. A. Decelle and L. L. Cheng, Eur. J. Nucl. Med. Mol. Imaging, 2013, 40, 60-71.
  • R Siegel
  • D Naishadham
R. Siegel, D. Naishadham and A. Jemal, CA-Cancer J. Clin., 2013, 63, 11-30.
  • P F Pinsky
  • B S Kramer
  • E D Crawford
  • R L Grubb
  • D A Urban
  • G L Andriole
  • D Chia
  • D L Levin
  • J K Gohagan
P. F. Pinsky, B. S. Kramer, E. D. Crawford, R. L. Grubb, D. A. Urban, G. L. Andriole, D. Chia, D. L. Levin and J. K. Gohagan, Urology, 2016, 68, 352-356.
  • H Lepor
H. Lepor, Rev. Urol., 2004, 6, S3-S10.
  • V A Moyer
V. A. Moyer, Ann. Intern. Med. Balanc., 2012, 157, 120. 10
  • T Kobus
  • A J Wright
  • E Weiland
  • A Heerschap
  • T W J Scheenen
T. Kobus, A. J. Wright, E. Weiland, A. Heerschap and T. W. J. Scheenen, Magn. Reson. Med., 2015, 73, 1-12.
  • M Truong
  • B Yang
  • D Jarrard
M. Truong, B. Yang and D. Jarrard, J. Urol., 2013, 189, 422-429.
  • A Riul
  • C A R Dantas
  • C M Miyazaki
  • O N Oliveira
A. Riul, C. a. R. Dantas, C. M. Miyazaki and O. N. Oliveira, Analyst, 2010, 135, 2481-2495.
  • L Lvova
  • E Martinelli
  • F Dini
  • A Bergamini
  • R Paolesse
  • C Di Natale
L. Lvova, E. Martinelli, F. Dini, A. Bergamini, R. Paolesse, C. Di Natale and A. D'Amico, Talanta, 2009, 77, 1097-1104.