Determination Of Tumor Markers Research Articles

Simultaneous determination of CYC and VEGF165 tumor markers based on immobilization of flavin adenine dinucleotide and thionine as probes on reduced graphene oxide-poly(amidoamine)/gold nanocomposite modified dual working screen-printed electrode

Herein, a novel electrochemical bi-aptasensor using green synthesized reduced graphene-poly(amidoamine)/gold nanocomposite (rGO-PAMAM/Aunano) as supporting matrix for covalent immobilization of flavin adenine dinucleotide (FAD) and thionine (Th) on the first (W1) and second (W2) surfaces of dual working electrode screen printed electrode has proposed. FAD and Th probes were immobilized by glutaraldehyde linker based on a reaction between primary amines (–NH2) of FAD and Th with –NH2 of rGO-PAMAM/Aunano modified dual working electrode for simultaneous determination of cytochrome c (CYC) and vascular endothelial growth factor (VEGF165) tumor markers. The principle response of proposed bi-aptasensor was based on the selective interaction of CYC with W1/rGO-PAMAM-FAD/Aunano/Anti-ptamerCYC and VEGF165 with W2/rGO-PAMAM-Th/Aunano/Anti-ptamerVEGF165, respectively. This selective interaction, leads to decrease of response currents of immobilized electrochemical probes of FAD and Th that have different formal potential (E0′). Electrochemical behavior of bi-aptasensor was studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The liner calibration curve for tumor markers determination was 2.5–320.0pM. The limit of detections (LOD) for CYC was 1.0pM and for VEGF165 was 0.7pM (3σ/S). The biomarker-aptamer dissociation constant (kd) was calculated based on the change in current to be 63.9pM for CYC/Anti-aptamerCYC and 38.4pM for VEGF165/Anti-aptamerVEGF165, respectively. This bi-aptasensor was used for the determination of VEGF165 and CYC in the human serum sample.

A SPR biosensor based on signal amplification using antibody-QD conjugates for quantitative determination of multiple tumor markers.

The detection of tumor markers is very important in early cancer diagnosis; however, tumor markers are usually present at very low concentrations, especially in the early stages of tumor development. Surface plasmon resonance (SPR) is widely used to detect biomolecular interactions; it has inherent advantages of being high-throughput, real-time, and label-free technique. However, its sensitivity needs essential improvement for practical applications. In this study, we developed a signal amplification strategy using antibody-quantum dot (QD) conjugates for the sensitive and quantitative detection of α-fetoprotein (AFP), carcinoembryonic antigen (CEA) and cytokeratin fragment 21-1 (CYFRA 21-1) in clinical samples. The use of a dual signal amplification strategy using AuNP-antibody and antibody-QD conjugates increased the signal amplification by 50-folds. The constructed SPR biosensor showed a detection limit as low as 0.1 ng/mL for AFP, CEA, and CYFRA 21-1. Moreover, the results obtained using this SPR biosensor were consistent with those obtained using the electrochemiluminescence method. Thus, the constructed SPR biosensor provides a highly sensitive and specific approach for the detection of tumor markers. This SPR biosensor can be expected to be readily applied for the detection of other tumor markers and can offer a potentially powerful solution for tumor screening.

Streptavidin-Functionalized Nitrogen Doped Graphene Platform for Sensitive Electrochemical Immunoassay of Tumor Marker

Tumor markers are biomacromolecules existing in blood or tissue, which are associated with cancer and whose measurement is useful in clinical diagnosis. The electrochemical immunoassay has attracted extensive attention due to its specific advantages such as high sensitivity, low cost, and easy handling. Here, a novel and highly efficient streptavidin-functionalized nitrogen doped graphene platform was proposed for sensitive electrochemical immunoassay of tumor marker. The biofunctionalized-nitrogen doped graphene platform shows large reactive surface area and excellent biocompatibility. The capture antibody can be efficiently immobilized on the biosensing platform surface based on the highly selective recognition of streptavidin to biotinylated antibody. Using carcinoembryonic antigen (CEA) as model analyte, the highly efficient electrochemical immunosensing shows a linear range from 0.02 to 12 ng/mL with a correlation coefficient of 0.9980. The limit of detection was calculated to be 0.01 ng/mL (S/N=3). This biofunctionalized-nitrogen doped graphene platform shows much better performance compared with the platform without nitrogen doped graphene (shown in Fig. 1). This work provides a promising application in the determination of various tumor markers.

Serum NSE, MMP-9 and HER2 extracellular domain are associated with brain metastases in metastatic breast cancer patients: predictive biomarkers for brain metastases?

Breast cancer (BC) is the second most common cause of brain metastases (BM). Predictive factors for BM have been widely studied in metastatic BC; however, there is no known serum tumor marker to accurately predict BM. Elevated serum S100ß protein and neuron-specific enolase (NSE) could reflect the brain damages induced by BM. Matrix metalloproteinase 9 (MMP-9) is involved in tumor invasion and metastatic dissemination, including BM. Also, HER2-amplified BC were shown to have a particular tropism for central nervous system (CNS). This study evaluated the correlation of these biomarkers with the presence of BM in metastatic BC patients. In this case-control study, 88 consecutive metastatic BC patients with BM (BM group) treated in our institution (2008-2015) were retrospectively selected, based on the availability of frozen serum samples for tumor marker determination. Patients were matched by age, tumor biology and number of previous metastatic chemotherapy lines to 162 metastatic BC patients without CNS involvement (control group). Serum NSE, MMP-9 and HER2 extracellular domain (ECD) levels were significantly higher in the BM group (p = 0.0051, p = 0.0062 and p = 0.0057, respectively). In multivariate analysis, serum HER2 and MMP-9 levels accurately discriminated patients with BM: odds ratios 4.4 (p < 0.001; 95%CI: 1.9-9.6) for HER2 ECD and 3.5 (p = 0.005; 95%CI: 1.5-8.4) for MMP-9. In multivariate analysis, HER2 ECD and NSE serum levels were independent prognostic factors in patients with BM. Serum HER2 ECD and MMP-9 appear to be associated with BM in metastatic BC patients. Their predictive value for BM still needs to be evaluated in further prospective studies.

Pt NPs and DNAzyme functionalized polymer nanospheres as triple signal amplification strategy for highly sensitive electrochemical immunosensor of tumour marker

Highly sensitive determination of tumour markers is the key for early diagnosis of cancer. Herein, triple signal amplification strategy resulting from polymer nanospheres, Pt NPs, and DNAzyme was proposed in the developed electrochemical immunosensor. First, electroactive polymer nanospheres were synthesized by infinite coordination polymerization of ferrocenedicarboxylic acid, which could generate strong electrochemical signals due to plentiful ferrocene molecules. Further, the polymer nanospheres were functionalized by Pt NPs and DNAzyme (hemin/G-quadruplex) with the ability of catalyzing H2O2, which contributes to enhance the electrochemical signals. The prepared conjugations were characterized by transmission electron microscope (TEM) and energy dispersive X-ray spectroscopy (EDX). And the process of preparation was monitored by zeta potential. Based on the sandwich-type immunoassay, the electrochemical immunosensor was constructed employing the conjugations as signal tags. Under optimal conditions, the DPV peak increased with the increasing of alpha fetal protein (AFP) concentration, and the linear range was from 0.1pgmL−1 to 100ngmL−1 with low detection limit of 0.086pgmL−1. Meanwhile, the designed immunosensor exhibited excellent selectivity and anti-interference property, good reproducibility and stability. More importantly, there were no significant differences in analyzing real clinical samples between designed immunosensor and commercial ELISA.

Neoplasms, as one of the causes of the syndrome of palpable abdominal tumor in children

Syndrome of palpable abdominal tumor in children is a difficult diagnostic problem. The difficulties associate with many disease entities that underlie this syndrome, often erased clinical picture and late referral to a doctor. In this article we will try to clarify the problems of diagnosis and treatment of exactly oncological diseases, as a cause of the syndrome palpable abdominal tumor. The vast majority of patients with complaints palpable education seek medical care to pediatricians or general practitioners. Prolongation of the diagnosis is often and directly associate with two factors: low oncological alertness by pediatricians (rarely by Pediatric Surgeons) and the lack of attention of parents to the initial manifestations of tumor in children. We have tried to describe the most characteristic symptoms inherent in the majority of tumors localized in the abdomen, the pelvis and the retroperitoneal space. Also there is information about on laboratory and instrumental methods of research used in the diagnosis of tumors, side by side the “routine” methods such as the complete blood count, abdominal ultrasound, in some cases, determination of specific tumor markers. There are the results of the comparative analysis and distinctive features of benign and malignant tumors of this localization are highlighted. Also the basic principles of the treatment of solid tumors in children are presented in this article. The article is focused primarily on all pediatricians, pediatric surgeons and general practitioners.

Follow-up Reality for Breast Cancer Patients - Standardised Survey of Patients and Physicians and Analysis of Treatment Data.

Introduction: Currently, about 360 000 breast cancer patients who could, after completion of their primary therapy, take advantage of follow-up options are living in Germany. Up to now very little is known about the extent to which the available options are used and as to how the follow-up reality is experienced and evaluated. Thus, an explorative examination among the patients and their physicians was undertaken. Patients and Methods: All patients who underwent surgery in a certified breast centre between 2007 and 2013 received a standardised questionnaire; at the same time the physicians responsible for the follow-up were invited to answer a standardised questionnaire. Results: 920 patients (response rate: 61 %) with a median age of 65 years (32-95) could be analysed. 99 % of the participants stated that they regularly attended follow-ups. The personal contact with the physician (mean value: 4.4) and the reassurance that the cancer disease had not recurred (mean value: 4.5) were described on a scale of 0 to 5 to be two of the most important factors of the follow-up. Deficits were expressed with regard to psychosocial care (70 %) and the perception and treatment of physical complaints (55 %). In addition, 105 physicians returned completed questionnaires (response rate: 12 %). For asymptomatic patients the physicians performed the following examinations most frequently: anamnesis (92 %), physical examination (87 %) as well as laboratory tests (63 %) and tumour marker determinations (40 %). Conclusion: On the whole it became clear that the vast majority of the patients took advantage of the follow-up options. From the patient's perspective the importance of the follow-up lies in contact to the physician and the comforting assurance that the breast cancer has not relapsed. Deficits are seen in the psychosocial care and the perception and treatment of physical impairments. Not recommended examinations were employed by a significant proportion of the surveyed physicians.

Displacement-type amperometric immunosensing platform for sensitive determination of tumour markers

The sensitive determination of carcino embryonie antigen (CEA)-a set of highly related glycoproteins involved in cell adhesion-is beneficial to the early diagnosis of colorectal cancer. In this study, a novel displacement-type amperometric immunosensing platform, based on the fact that glucose and Alizarin Red S (ARS) compete for phenylboronic acid bindng sites, was projected for sensitive detection of tumour marker (CEA, used as a model) on a PAMAM dendrimer-encapsulated nanogold (PAMAM-Au)-functionlized sensing interface. Firstly, 4−mercaptophenylboronic acid (S-PBA) was assembled onto the PAMAM-Au via the S-Au interaction, and then ARS was immobilized by S-PBA binding of cis-diol moieties, which was dropped on the surface of glassy carbon electrode as sensing platform to combine antibody. Meanwhile, amylase modified gold nanoparticles were employed as labels. Accompanying the sandwich immunoassay, the carried amylase could hydrolyze amylose into glucose, and the displacement-type format was triggered due to the stronger adhesion between glucose and PBA, which resulted in the change of electrochemical signals due to the decrease of ARS (as an electron mediator). Under optimal conditions, the SWV signals were related to the concentration of CEA, indicating a certain proportional relation in a range of 0.01~50ngmL−1 with a detection limit (LOD) of 0.003ngmL−1. Intra- and inter-assay coefficients of variation were below 10%, respectively. In addition, the methodology showed good accordance with a commercialized enzyme-linked immunosorbent assay (ELISA) method.

How should we monitor boys with testicular microlithiasis?

ABSTRACTTesticular microlithiasis (TM), a rare condition characterized by calcification within the seminiferous tubules, is associated with benign and malignant disorders of the testis. We review current practices of following up pediatric patients diagnosed TM incidentally on scrotal ultrasonography (US). We analyzed retrospectively patient characteristics, family history, indications for US, pathological features, US findings, outcome, and follow-up. At our institution, 2875 scrotal US examinations were performed on 2477 children with various scrotal complaints from 2008 to 2015. Testicular microlithiasis was detected in 81 patients (i.e., an incidence of 3.27%). Every 6 months, each patient underwent a clinical and ultrasonographic evaluation as well as serum tumor markers determination to detect a potential malignancy. Seventy-eight patients who had undergone scrotal US at least twice were included in this study. We evaluated the US studies for the type of TM (diffuse and focal) and change in follow-up studies. Testicular microlithiasis was typically diffuse (n = 56, 71.8%) and bilateral (n = 45, 57.7%), and it was detected the most frequently in the 9–11-year age group (27 patients, 34.6%). The most common comorbid conditions included undescended testes (31 patients, 39.7%) and hydrocele (11 patients, 14.1%). We found that serum tumor markers were within normal limits both at diagnosis and upon follow-up. No testicular tumors or new abnormal symptoms developed during the clinical follow-up. There is no convincing evidence that TM alone is premalignant in a pediatric population. In terms of follow-up, we advise regular self-examinations and annual US in the absence of risk factors.

GASTRIC CANCER TUMOR MARKERS

Gastric cancer remains an aggressive malignancy responsible for a high number of deaths annually. An important method used in order to determine the response to treatment, follow-up and detection of recurrence in association with imagistic examinations remains laboratory determination of tumor markers. The most common used tumor markers in patients diagnosed with gastric cancer are CA 72-4, CEA, CA 19-9.

Appropriate use of tumour biomarkers for treatment with innovative drugs: A retrospective study.

Performing randomised clinical trials to address the clinical usefulness of predictive and prognostic tumour markers is a complex process for several reasons, and observational experiences may thus play an important role. The present study performed an observational retrospective analysis in Area Vasta Romagna, Italy, collecting information on tumour marker determination in 760 consecutive patients who started a new line of anticancer therapy between January and June 2010. The determination of well-known biomarkers was requested for all gastrointestinal stromal tumour (GIST) patients (n=13) and for almost all breast cancer patients (n=369), and targeted therapies were consequently prescribed. Conversely, Kirsten rat sarcoma viral oncogene homolog (KRAS) determination in colon cancer patients (n=177) was requested in ~50% of advanced cases, while epidermal growth factor receptor (EGFR) determination was required in slightly more than 30% of the same patients. EGFR and KRAS determinations were requested in only 15% and 7.5% of non-small cell lung cancer (NSCLC) patients (n=201), respectively. There would appear to be greater appropriateness of tumour marker determination for breast cancer and GISTs than for colon cancer and NSCLC. Resources can be further optimised by standardising tumour marker determinations in terms of the timing of requests and the consequent use of the results for tailored treatment planning.

CBM-07SERUM NSE, MMP-9 AND HER2 ARE PREDICTIVE OF BRAIN METASTASES IN METASTATIC BREAST CANCER PATIENTS

BACKGROUND: Breast cancer (BC) is the second leading cause of brain metastases (BM). Predictive factors for BM have been widely studied in metastatic BC; however, there is no known serum tumor marker to accurately predict BM in this population. Serum levels of protein S100, an astrocytic marker, are associated with stroke severity. Neuron Specific Enolase (NSE), a neuronal marker, has been associated with BM prognosis in lung cancer. Elevated serum levels of these markers could reflect the brain damages induced by BM. Matrix Metalloproteinase 9 (MMP-9) is involved in tumor invasion and metastatic dissemination, including BM. Finally, it has been shown that HER2-amplified breast tumors have a particular tropism for central nervous system. This study evaluates the predictive value of these four markers for BM in a population of metastatic BC patients. METHODS: In this case-control study, 88 consecutive BC patients with BM (cases) treated at the Montpellier Cancer Institute (2008-2015) were retrospectively selected, based on the availability of frozen serum samples for tumor markers determination. Cases were matched by age, tumor biology and number of previous metastatic treatment lines to 162 patients with metastatic BC but without CNS involvement (controls). RESULTS: Serum HER2, NSE and MMP-9 levels were significantly higher in cases than in controls (p= 0.0057, p = 0.0051 and p = 0.0062, respectively). Median HER2 (ng/ml) was 21.1 in cases compared to 12.3 in controls; median NSE (µg/l) was 10.8 compared to 8.70 in controls; median MMP-9 (ng/µl) was 422.9 in cases compared to 320.5 in controls. In multivariate analysis, serum HER2 and MMP-9 levels accurately discriminated cases from controls: odd ratio 4.4 (p = 0.000; 95%CI 1.9-9.6) for HER2 and 3.5 (p = 0.005; 95%CI 1.5-8.4) for MMP-9. CONCLUSIONS: Serum HER2 and MMP-9 seem to be predictive of BM in metastatic BC patients. These results need to be validated in further larger prospective studies.

Is professional prescription of a commercially derived dietary supplement in colectomysed patients necessary?

IntroductionColorectal cancers are the second most common cause of mortality in the USA, Western Europe and also Hungary. After the removal of a tumor, cancer predisposition still remains, therefore secondary prevention is needed. Several reports are known about the effects of nutritional supplements in the improvement of patient life quality. Therefore the question arises whether natural food supplement products with several bioactive agents can modify immune reactivity or influence redox homeostasis. MethodsIn the present study we report on the negative output of the commercially derived dietary supplement “Vegetable and fruit color compound concentrates OÉTI 45/É sample” in colectomysed patients. Quantitative analysis of anthocyanins and flavonoids in this dietary supplement, was carried out using HPLC-DAD-ESI–MS/MS. Caucasian volunteers (N=26) were treated with the dietary supplement for 3 months 5–10 years after their colectomy. The healthy control volunteers (N=10) of both genders received the supplement the same way. The dose was 2×3g/day. Ultrasonography, routine laboratory tests (30 parameters), tumor marker (AFP, CEA, CA19-9, PSA) determinations and redox parameters (SOD, GSHPx, HbA1c, reducing power, chemiluminescence intensity) were carried out for each person. ResultsDiet-related bioactive compounds were intensively examined in vitro, although in vivo and in vitro effects are different and the mode of actions in vivo are not yet known in detail. Tentative identification of dietary supplements based on mass spectrometry data for published constituents of plants, twenty anthocyanins and flavonoid glycosides were identified.Several routine laboratory parameters were not altered after treatment compared to start time data in colectomysed patients and control volunteers. The treatment did not change the tumor marker levels significantly, but in each case the values were elevated in examined groups. Redox parameters of colectomysed patients showed strengthened free radical reactions, namely rebound effect against antioxidant excess, although tendency was observed in controls as well. Anti-inflammatory effects of the natural product was not clearly observed. ConclusionToday, there are countless products on the market, thus experts in healthcare, doctors, pharmacists and dieticians should have adequate knowledge of dietary supplements, and how can they become important tools for a healthy lifestyle. SupportETT 02/02/2009.

Diagnostics and treatment improving of functional ovarian cysts

Functional ovarian cysts are benign tumour retention formations formed from the natural structures of the ovary – follicle or yellow body. In 50% of cases cysts are asymptomatic and self-liquidated. In the absence of functional cyst self-destruct in the first menstrual cycle after treatment it should be revealing.Functional cysts are divided into follicular cysts, corpus luteum cyst, paraovarian cysts.Diagnosis consists of analysing history, general examination, gynaecological examination, clinical laboratory tests (including advanced analysis of blood, determination of C-reactive protein, appropriate biochemical if it need, compulsory bacterioscopic and bacteriological examination of vaginal discharge) and special methods of diagnosing ovarian tumors (ultrasound, computed or magnetic resonance tomography, determination of tumor markers, human chorionic gonadotropin, α-fetoprotein, hormones analysis, endoscopy).Clinical management of patients with functional cysts in reproductive and perimenopausal age includes the following options. In asymptomatic disease in three menstrual cycles conducted surveillance of ultrasound control and preventive measures against cyst recurrence. Conservative treatment is used after determining the causes of disease for persistent cysts. Therapeutic measures include anti-inflammation therapy, hormonal and anti-adhesion therapy. While cysts maintaining after conservative treatment for three menstrual cycles the laparoscopy is used for removing formations.Treatment is more successful when combined allopathic, homeopathic and phytotherapy. Most pathogenic provided in the treatment of functional ovarian cysts is an herbal preparation mastodynon. Mastodynon is a complex drug containing standardized herbal ingredients with depressing effect on inflammatory cytokines, helps eliminate hormonal imbalance caused by hyperestrogenia of follicular cysts (endometrial hyperplasia). In addition, the main component of mastodynon – Vitex Agnus Castus – promotes the elimination of the latent hyperprolactinemia, which in turn causes the hyperestrogenia development.After the disappearance of the cyst to prevent recurrence of reproductive age with elevated levels of follicle stimulating hormone and luteinizing hormone the use of combined oral contraceptives for four to six menstrual cycles is needed.Surgery treatment indicated if there is complication (torsion, rupture, suppuration).

Prostate cancer tumor markers

Prostatic cancer represents an important health problem worldwide, being the third most common malignancy in men older than 55 years, after pulmonary and colon cancer. In early stages prostatic cancer remains hard to be diagnosed at clinical or imagistical studies, the most efficient way to detect it being based on the determination of tumor markers. This is a literature review of the largest studies conducted on the theme of prostatic tumor markers.

A study of CA-125 in patients with pleural effusion

A significant concern of physicians treating patients with pleural effusion is to rule out a malignant etiology, which, in the majority of series, is the first cause of pleural exudates. Determination of tumor markers in serum and pleural fluid has been proposed as a nonaggressive means of establishing a diagnosis of pleural malignancy. Cancer antigen 125 (CA-125) is not a specific tumor marker and it is synthesized by normal and malignant cells of different origins. Recently, it has been shown that various diseases are associated with increased CA-125 levels, especially in the presence of serosal fluid. The aim of this study was to determine the level of serum and pleural fluid CA-125 to evaluate its value as a marker for differentiation between different types of pleural effusion. The study was carried out on 30 patients with pleural effusion of different etiologies. They were further subdivided into two groups: exudates and transudates; the levels of both serum and pleural fluid CA-125 were evaluated. In terms of pleural CA-125, there was a statistically significant increase in the exudative subgroup compared with transudative subgroup. Furthermore, it was found that malignant effusion was observed more frequently compared with benign effusion and tuberculosis was observed more frequently in comparison with other infections. The highest level of pleural fluid CA-125 was found in malignancy, followed by tuberculosis, and so pleural fluid CA-125 can be used as a marker for the diagnosis of pleural effusion. Egypt J Broncho 2015 9:283–286

Biopsy for liver cancer: How to balance research needs with evidence‐based clinical practice

Biopsy for liver cancer: How to balance research needs with evidence‐based clinical practice

Molecular markers for breast cancer: prediction on tumor behavior.

Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical management in cancer patients, assisting in diagnostic, staging, evaluation of therapeutic response, detection of recurrence and metastasis, and development of new treatment modalities. In this context, this review aims to discuss the main tumor markers in breast carcinogenesis. The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented. Furthermore, this review shows the new molecular targets in breast cancer: CXCR4, caveolin, miRNA, and FOXP3, as promising candidates for future development of effective and targeted therapies, also with lower toxicity.

Cocarcinogenic Effects of Intrahepatic Bile Acid Accumulation in Cholangiocarcinoma Development

Bile acid accumulation in liver with cholangiolar neoplastic lesions may occur before cholestasis is clinically detected. Whether this favors intrahepatic cholangiocarcinoma development has been investigated in this study. The E. coli RecA gene promoter was cloned upstream from Luc2 to detect in vitro direct genotoxic ability by activation of SOS genes. This assay demonstrated that bile acids were not able to induce DNA damage. The genotoxic effect of the DNA-damaging agent cisplatin was neither enhanced nor hindered by the hepatotoxic and hepatoprotective glycochenodeoxycholic and glycoursodeoxycholic acids, respectively. In contrast, thioacetamide metabolites, but not thioacetamide itself, induced DNA damage. Thus, thioacetamide was used to induce liver cancer in rats, which resulted in visible tumors after 30 weeks. The effect of bile acid accumulation on initial carcinogenesis phase (8 weeks) was investigated in bile duct ligated (BDL) animals. Serum bile acid measurement and determination of liver-specific healthy and tumor markers revealed that early thioacetamide treatment induced hypercholanemia together with upregulation of the tumor marker Neu in bile ducts, which were enhanced by BDL. Bile acid accumulation was associated with increased expression of interleukin (IL)-6 and downregulation of farnesoid X receptor (FXR). Bile duct proliferation and apoptosis activation, with inverse pattern (BDL > thioacetamide + BDL >> thioacetamide vs. thioacetamide > thioacetamide + BDL > BDL), were observed. In conclusion, intrahepatic accumulation of bile acids does not induce carcinogenesis directly but facilitates a cocarcinogenic effect due to stimulation of bile duct proliferation, enhanced inflammation, and reduction in FXR-dependent chemoprotection. This study reveals that bile acids foster cocarcinogenic events that impact cholangiocarcinoma.

A label-free immunosensor based on graphene nanocomposites for simultaneous multiplexed electrochemical determination of tumor markers

Here we prepared a label-free electrochemical immunosensor employing indium tin oxide (ITO) sheets as working electrodes and graphene nanocomposites as supporting matrix for simultaneous determination of carcinoembryonic antigen (CEA) and α-fetoprotein (AFP). Reduced graphene oxide/thionine/gold nanoparticles nanocomposites were synthesized and coated on ITO for the immobilization of anti-CEA while reduced graphene oxide/Prussian Blue/gold nanoparticles were used to immobilize anti-AFP. The immunosensor determination was based on the fact that due to the formation of antibody–antigen immunocomplex, the decreased response currents of thionine and Prussian Blue were directly proportional to the concentrations of corresponding antigens. Experimental results revealed that the multiplexed immunoassay enabled the simultaneous determination of CEA and AFP with linear working ranges of 0.01–300ngmL−1. The limit of detections for CEA is 0.650pgmL−1 and for AFP is 0.885pgmL−1. In addition, the methodology was evaluated for the analysis of clinical serum samples and received a good correlation with the enzyme linked immunosorbent assay.