Prostate Cancer Antigen Research Articles

Intérêt du test PCA3 avant une première série de biopsies prostatiques négatives : 5 ans de suivi

We report a 5-year follow-up of a cohort of patients who underwent a first prostate biopsy following a prostate cancer antigen 3 (PCA3) test. We reviewed consecutive patients who had in 2008 a single urinary PCA3 test using the Gen-Probe® assay before a first prostate biopsy for a prostate-specific antigen (PSA) between 3 and 20ng/mL and/or a suspicious digital rectal examination. PCA3 performances were analyzed in 2008 and then in 2013 after taking into account the results of repeat biopsies. At initial biopsy in 2008, among the 125 patients study cohort, prostate cancer was diagnosed in 47 patients (37.6%). Abnormal digital rectal exam, PSA density, prostate volume and PCA3 score were significantly associated with prostate cancer diagnosis. PCA3 area under the curve of the receiver operating curve was 0.67 [95%CI: 0.57-0.76] with an optimal threshold of PCA3 in this sample of 24 units. During the 5-year follow-up, among the 78 patients with a negative prostate biopsy in 2008, 23 (29.5%) had a repeat prostate biopsy of whom 14 were diagnosed with prostate cancer. PCA3 score measured in 2008 was associated with prostate cancer diagnosis (P=0.002). All 9 patients with a negative repeat prostate biopsy had a PCA3 score below the cut-off while this was the case in only 2 patients among the 14 with a positive repeat prostate biopsy. The results of a single PCA3 test before a first prostate biopsy seems to be a useful aid in deciding whether to perform a repeat biopsy. 4.

An inconvenient truth: at least three prostate-specific antigen-based screening cycles are needed to reduce subsequent prostate cancer incidence

The pros and cons of using prostate-specific antigen (PSA) for prostate cancer (PC) screening have been debated in terms of mortality reduction versus overdiagnosis and overtreatment as well as the overall balance of quality-of-life effects and cost-effectiveness. Because PSA is not a PC-specific biomarker, the use of PSA as a biomarker for PC has several limitations. In addition, PSA levels are influenced by several factors, including age, acute prostatitis, ejaculation, catheterization, and certain medications. Furthermore, there is no precise value indicative of a lack of PC risk, and PSA levels cannot distinguish between indolent and aggressive disease, particularly at PSA levels below 20 ng/mL. In addition, approximately 15% men with serum PSA levels below 4 ng/mL are at risk for PC (1).

Current Insights into Long Non-Coding RNAs (LncRNAs) in Prostate Cancer.

The importance of long non-coding RNAs (lncRNAs) in the pathogenesis of various malignancies has been uncovered over the last few years. Their dysregulation often contributes to or is a result of tumour progression. In prostate cancer, the most common malignancy in men, lncRNAs can promote castration resistance, cell proliferation, invasion, and metastatic spread. Expression patterns of lncRNAs often change during tumour progression; their expression levels may constantly rise (e.g., HOX transcript antisense RNA, HOTAIR), or steadily decrease (e.g., downregulated RNA in cancer, DRAIC). In prostate cancer, lncRNAs likewise have diagnostic (e.g., prostate cancer antigen 3, PCA3), prognostic (e.g., second chromosome locus associated with prostate-1, SChLAP1), and predictive (e.g., metastasis-associated lung adenocarcinoma transcript-1, MALAT-1) functions. Considering their dynamic role in prostate cancer, lncRNAs may also serve as therapeutic targets, helping to prevent development of castration resistance, maintain stable disease, and prohibit metastatic spread.

Low PCA3 expression is a marker of poor differentiation in localized prostate tumors: exploratory analysis from 12,076 patients

BackgroundProstate cancer antigen 3 (PCA3) is a prostate cancer diagnostic biomarker that has been clinically validated. The limitations of the diagnostic role of PCA3 in initial biopsy and the prognostic role are not well established. Here, we elucidate the limitations of tissue PCA3 to predict high grade tumors in initial biopsy.ResultsPCA3 has a bimodal distribution in both biopsy and radical prostatectomy (RP) tissues, where low PCA3 expression was significantly associated with high grade disease (p<0.001). PCA3 had a poor performance of predicting high grade disease in initial biopsy (GS≥8) with 55% sensitivity and high false negative rates; 42% of high Gleason (≥8) samples had low PCA3. In RP, low PCA3 is associated with adverse pathological features, clinical recurrence outcome and greater probability of metastatic progression (p<0.001).Materials and MethodsA total of 1,694 expression profiles from biopsy and 10,382 from RP patients with high risk tumors were obtained from the Decipher Genomic Resource Information Database (GRIDTM)prostate cancer database. The primary clinical endpoint was distant metastasis-free survival for RP and high Gleason grade for biopsy. Logistic regression analyses and Cox proportional hazards models were used to evaluate the association of PCA3 with clinical variables and risk of metastasis.ConclusionsThere is high prevalence of high grade tumors with low PCA3 expression in the biopsy setting. Therefore, urologists should be warned that using PCA3 as stand-alone test may lead to high rate of under-diagnosis of high grade disease in initial biopsy setting.

Racial Variation in the Utility of Urinary Biomarkers PCA3 and T2ERG in a Large Multicenter Study

To our knowledge it is unknown whether urinary biomarkers for prostate cancer have added utility to clinical risk calculators in different racial groups. We examined the utility of urinary biomarkers added to clinical risk calculators for predicting prostate cancer in African American and nonAfrican American men. Demographics, PCPT (Prostate Cancer Prevention Trial) risk scores, data on the biomarkers data PCA3 (prostate cancer antigen 3) and T2ERG (transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog gene fusion), and biopsy pathology features were prospectively collected on 718 men as part of EDRN (Early Detection Research Network). Utility was determined by generating ROC curves and comparing AUC values for the baseline multivariable PCPT model and for models containing biomarker scores. PCA3 and T2ERG added utility for the prediction of prostate cancer and clinically significant prostate cancer when combined with the PCPT Risk Calculator. This utility was seen in nonAfrican American men only for PCA3 (AUC 0.64 increased to 0.75 for prostate cancer and to 0.69-0.77 for clinically significant prostate cancer, both p <0.001) and for T2ERG (AUC 0.64-0.74 for prostate cancer, p <0.001, and 0.69-0.73 for clinically significant prostate cancer, p = 0.029). African American men did not have an added benefit with the addition ofbiomarkers, including PCA3 (AUC 0.75-0.77, p = 0.64, and 0.65-0.66, p=0.74)and T2ERG (AUC 0.75-0.74, p = 0.74, and 0.65-0.64, p = 0.88), forprostate cancer and clinically significant prostate cancer, respectively. Limitations include the small number of African American men (72). The post hoc subgroup analysis nature of the study limited findings to being hypothesis generating. As novel biomarkers are discovered, clinical utility should be established across demographically diverse cohorts.

STEAP-1: A Potential Biomarker, Promising Target?

STEAP1 is one of six-transmembrane epithelial antigen of prostate (STEAP) highly expressed in human prostate cancer and is up-regulated in multiple cancers, including bladder, colon, breast, Ewing and lung cancers. Immunohistochemical analysis demonstrates significant STEAP1 expression at the intercellular communication between adjacent cells suggesting that this antigen must be a channel, or a transport protein indicating its potential role in tumor cell intercellular communication increasing the potential of STEAP1 as a diagnostic, prognostic, prophylactic and/or therapeutic target for new immunotherapeutic strategies. In prostate cancer, overexpression relates adenocarcinoma and prostatic intraepithelial neoplasia scores suggest that STEAP1 could be involved in tumor initiation and progression and may be of clinical usefulness in early disease diagnosis. Also, STEAP1 can serve as a biomarker of worse prognosis because of its association with higher Gleason score, seminal vesicle invasion, biochemical recurrence, and worse outcome. Therapeutically, STEAP1 is one of a few prostate cancer antigens that meet the appropriate criteria and represent an attractive target for antibody cancer therapy. It can be a target of anti-tumor CD8, or serve as a tool for vaccination as shown by xenograft models and phases I/II studies. STEAP1 could also serve as a new marker of tumor angiogenesis in lung cancer, indicate for occult residual tumor cells in patients with Ewing Sarcoma and also be used as a cell surface antigen for the development of breast cancer immunotherapy. The standardization of its evaluation as well as the validation through randomized trials would be necessary.

Genetic variation of the PSCA gene (rs2294008) is not associated with the risk of prostate cancer.

Prostate stem cell antigen ( PSCA ) is a cell-membrane glycoprotein consisting of 123 amino acids and highly expressed in the prostate, but there have been few reports on the relationship between rs2294008 of PSCA and prostate cancer in the literature. Therefore, we evaluated the association between rs2294008 and the risk of prostate cancer. A total of 240 prostate cancer patients and 306 controls (patients with benign prostatic hyperplasia) were enrolled. Genotype analysis of rs2294008 of PSCA was performed using PCR. Logistic regression analysis was performed according to the genotype of PSCA rs2294008. We found that CT and TT genotypes were associated with an insignificant risk of prostate cancer compared with the CC genotype ( P = 0.627 and 0.397, respectively). In addition, there was no significant difference in rs2294008 according to clinicopathological parameters, such as age, Gleason score, prostate-specific antigen (PSA), stage, and metastasis in prostate cancer ( P >0.05 for each). Age, Gleason score, PSA, pathologic stage, and metastasis did not modify the association between PSCA and the risk of prostate cancer (each P >0.05 for each). Taken together, the genetic polymorphism of PSCA rs2294008 was not associated with the risk of prostate cancer. Our results suggest that rs2294008 may not play a role in prostate carcinogenesis.

The role of the percentage free PSA in the diagnosis of prostate cancer in Blacks: Findings in indigenous West African men using TRUS guided biopsy

IntroductionIn Western and Asian literature, the measurement of percentage free prostate specific antigen (%fPSA) has been known to enhance the predictive role of total prostate specific antigen (tPSA) in early prostate cancer (Ca-P) detection. Relationship between the tPSA and Ca-P are known to be influenced by race. To the best of our knowledge, the relationship between %fPSA and Ca-P has not been studied in sub-Saharan Africa using current established biopsy protocol. ObjectiveTo evaluate the usefulness of %fPSA in indigenous West African men and determine the appropriate cut-off values that may be used as indication for prostate biopsy in men with tPSA of 4–10ng/ml. Subjects and methodsA total 169 consecutive patients with tPSA of 4–10ng/ml with non-suspicious findings on digital rectal examination (DRE) had a transrectal ultrasound (TRUS) guided 10-core prostate biopsy. The technique of PSA analysis was the Access hybritech assay technique using the Beckman's Access autoimmuno analyser. The rates of prostate cancer in different %fPSA ranges were evaluated. Receiver operating characteristic curve (ROC) was used to evaluate the efficiency of %fPSA in the diagnosis of prostate cancer. ResultsA reduction %fPSA was associated with a higher detection rate of Ca-P. There was a 62% prevalence of Ca-P with %fPSA≤10% while there was a zero prevalence in patients with fPSA above 20%. At a %fPSA cut off of 20% the sensitivity and specificity were 100% and 45%, respectively. Using the ROC curve, the area under the curve (AUC) was 0.76 while the ROC decision plot showed that a %fPSA cut off 15% was associated with the highest ability to discriminate between benign and malignant diseases. ConclusionThe %fPSA is an effective discriminating tool in determining the need for prostate biopsy in indigenous West African men with PSA 4–10ng/ml. A cut off of 15% was associated with the highest performance.

Blood-based and urinary prostate cancer biomarkers: a review and comparison of novel biomarkers for detection and treatment decisions.

The diagnosis of prostate cancer (PCa) is currently based on serum PSA testing and/or abnormal digital rectal examination and histopathologic evaluation of prostate biopsies. The main drawback of PSA testing is the lack of specificity for PCa. To improve early detection of PCa more specific biomarkers are needed. In the past few years, many new promising biomarkers have been identified; however, to date, only a few have reached clinical practice. In this review, we discuss new blood-based and urinary biomarker models that are promising for usage in PCa detection, follow-up and treatment decision-making. These include Prostate Health Index (PHI), prostate cancer antigen 3 (PCA3), four-kallikrein panel (4K), transmembrane protease serine 2-ERG (TMPRSS2-ERG), ExoDx Prostate Intelliscore, SelectMDx and the Mi-Prostate score. Only few head-to-head studies are available for these new fluid-based biomarkers and/or models. The blood-based PHI and urinary PCA3 are two US Food and Drug Administration-approved biomarkers for diagnosis of PCa. In the second part of this review, we give an overview of published studies comparing these two available biomarkers for prediction of (1) PCa upon prostate biopsy, (2) pathological features in radical prostatectomy specimen and (3) significant PCa in patients eligible for active surveillance. Studies show opposing results in comparison of PHI with PCA3 for prediction of PCa upon initial and repeat prostate biopsy. PHI and PCA3 are able to predict pathological findings on radical prostatectomy specimen, such as tumor volume and Gleason score. Only PHI could predict seminal vesicle invasion and only PCA3 could predict multifocality. There is some evidence that PHI outperforms PCA3 in predicting significant PCa in an active surveillance population. Future research should focus on independent validation of promising fluid-based biomarkers/models, and prospective comparison of biomarkers with each other.

Abstract A010: A novel DNA vaccine targeting fibroblast activation protein (FAP) breaks tolerance and synergizes with anticancer immune therapy in mice

Abstract Fibroblast activation protein (FAP) is a membrane-bound enzyme with gelatinase and peptidase activity that is up-regulated in cancer-associated fibroblasts in over 90% of human carcinomas. Previous studies have shown that ablation of FAP-expressing cells from transgenic mice attenuates tumor growth and synergizes with other immune therapies such as immune checkpoint blockade. Groups have additionally shown that T cells expressing chimeric antigen receptors targeting FAP slow tumor progression; however, in some mouse strains these CARs cause lethal toxicity. There is therefore a need to develop safer therapies targeting FAP. In this study we designed a novel consensus-based FAP DNA vaccine to help break tolerance. We hypothesized that this FAP vaccine could break tolerance and synergize with other immunotherapies to induce anti-tumor immunity without causing overt toxicity. Upon delivery of our FAP DNA vaccine intramuscularly followed by electroporation (EP), we detected IFN-γ and TNF-α CD8 T cell responses (p&amp;lt;0.05), and TNF-α CD4 responses (p&amp;lt;0.05) against native mouse FAP peptides, indicating that our vaccine is capable of breaking tolerance. Furthermore, we detected cytotoxic CD107a/IFNγ/T-bet triple-positive CD8 T cells that are reactive to native FAP peptides (p&amp;lt;0.05). In a prostate cancer model, vaccination with FAP alone or the prostate cancer antigen PSMA alone did not significantly alter tumor growth. However, vaccination with a combination of FAP and PSMA significantly attenuated tumor growth (p&amp;lt;0.0005), with final tumor volumes that were approximately 9 times smaller than tumors in naïve mice. Thus, our results support the use of FAP vaccines to target the tumor microenvironment in combination with immune therapies targeting the tumor cells themselves. We are investigating additional combination therapies with our FAP vaccine to modulate tumor infiltrating lymphocytes and to broaden responses to additional tumor antigens. Citation Format: Elizabeth Duperret, Dylan Ammons, Megan C. Wise, Jian Yan, Laurent M. Humeau, David B. Weiner. A novel DNA vaccine targeting fibroblast activation protein (FAP) breaks tolerance and synergizes with anticancer immune therapy in mice [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A010.

Real-time electrical detection of epidermal skin MoS2 biosensor for point-of-care diagnostics

Various approaches have been proposed for point-of-care diagnostics, and in particular, optical detection is preferred because it is relatively simple and fast. At the same time, field-effect transistor (FET)-based biosensors have attracted great attention because they can provide highly sensitive and label-free detection. In this work, we present highly sensitive, epidermal skin-type point-of-care devices with system-level integration of flexible MoS2 FET biosensors, read-out circuits, and light-emitting diode (LEDs) that enable real-time detection of prostate cancer antigens (PSA). Regardless of the physical forms or mechanical stress conditions, our proposed high-performance MoS2 biosensors can detect a PSA concentration of 1 pg·mL–1 without specific surface treatment for anti-PSA immobilization on the MoS2 surface on which we characterize and confirm physisorption of anti-PSA using Kelvin probe force microscopy (KPFM) and tapping-mode atomic force microscopy (tm-AFM). Furthermore, current modulation induced by the binding process was stably maintained for longer than 2–3 min. The results indicate that flexible MoS2-based FET biosensors have great potential for point-of-care diagnostics for prostate cancer as well as other biomarkers.

Inducible expression of cancer-testis antigens in human prostate cancer.

Immune tolerance to self-antigens can limit robust anti-tumor immune responses in the use of tumor vaccines. Expression of novel tumor associated antigens can improve immune recognition and lysis of tumor cells. The cancer-testis antigen (CTA) family of proteins has been hypothesized to be an ideal class of antigens due to tumor-restricted expression, a subset of which have been found to induce antibody responses in patients with prostate disease. We demonstrate that CTA expression is highly inducible in five different Prostate Cancer (PC) cell lines using a hypomethylating agent 5-Aza-2′-deoxycytidine (5AZA) and/or a histone deacetylase inhibitor LBH589. These CTAs include NY-ESO1, multiple members of the MAGE and SSX families and NY-SAR35. A subset of CTAs is synergistically induced by the combination of 5AZA and LBH589. We developed an ex vivo organ culture using human PC biopsies for ex vivo drug treatments to evaluate these agents in clinical samples. These assays found significant induction of SSX2 in 9/9 distinct patient samples and NY-SAR35 in 7/9 samples. Further, we identify expression of SSX2 in circulating tumor cells (CTC) from patients with advanced PC. These results indicate that epigenetic modifying agents can induce expression of a broad range of neoantigens in human PC and may serve as a useful adjunctive therapy with novel tumor vaccines and checkpoint inhibitors.

Snail-activated long non-coding RNA PCA3 up-regulates PRKD3 expression by miR-1261 sponging, thereby promotes invasion and migration of prostate cancer cells.

Rapidly accumulated evidence has shown that long non-coding RNA (lncRNAs) disregulation is involved in human tumorigenesis in many cancers, including prostate cancer (PCa). LncRNAs can regulate essential pathways that contribute to tumor initiation and progression with tissue specificity, which suggests that lncRNAs could be valuable biomarkers and therapeutic targets. Prostate cancer antigen 3 (PCA3), also known as differential display code 3 (DD3), is one such lncRNA that maps to chromosome 9q21-22. PCA3 expression is highly specific to PCa. In the present study, the level of PCA3 expression in prostate cancer cells was reduced by small interfering RNA (siRNA). Subsequently, the ability of LNCaP cell proliferation, invasion, and migration of PCa was compromised both in vivo and in vitro with the occurrence of cell autophagy. Recently, a novel regulatory mechanism has been proposed in which RNAs cross talk via competing with the shared microRNAs (miRNAs). In addition, lncRNAs can directly interact with RNA-binding proteins and then bind to the gene promoter region to further regulate gene expression. The proposed competitive endogenous RNAs mediate the bioavailability of miRNAs on their targets, thus imposing another level of post-transcriptional regulation. Here, we demonstrated that binding of Snail to the promoter region of PCA3 could activate the expression of PCA3. Down-regulation of PCA3 by silencing could increase the expression of the miRNA-1261, which then targeted at the PRKD3 gene (protein kinase D3) through competitive sponging. In summary, these results suggest that the transcription factor, Snail, activated the expression of lncRNA PCA3, which could inhibit the translation of PRKD3 protein via competitive miR-1261 sponging, and thus high expression of PRKD3 further promoted invasion and migration of prostate cancer.

Biparametric 3T Magentic Resonance Imaging for prostatic cancer detection in a biopsy-naïve patient population: a further improvement of PI-RADS v2?

ObjectivesTo prospectively determine the diagnostic accuracy of a biparametric 3T magnetic resonance imaging protocol (BP-MRI) for prostatic cancer detection, compared to a multiparametric MRI protocol (MP-MRI), in a biopsy naïve patient population. MethodsEighty-two untreated patients (mean age 65±7.6years) with clinical suspicion of prostate cancer and/or altered prostate-specific antigen (PSA) levels underwent a MP-MRI, including T2-weighted imaging, diffusion-weighted imaging (with the correspondent apparent diffusion coefficient maps) and dynamic contrast enhanced sequence, followed by prostate biopsy. Two radiologists reviewed both the BP-MRI and the MP-MRI protocols to establish a radiological diagnosis. Receiver operating characteristics curves were obtained to determine the diagnostic performance of the two protocols. ResultsThe mean PSA level was 8.8±8.1ng/ml. A total of 34 prostatic tumors were identified, with a Gleason score that ranged from 3+3 to 5+4. Of these 34 tumors, 29 were located within the peripheral zone and 5 in the transitional zone. BP-MRI and MP-MRI showed a similar performance in terms of overall diagnostic accuracy, with an area under the curve of 0.91 and 0.93, respectively (p=n.s.). ConclusionsBP-MRI prostate protocol is feasible for prostatic cancer detection compared to a standard MP-MRI protocol, requiring a shorter acquisition and interpretation time, with comparable diagnostic accuracy to the conventional protocol, without the administration of gadolinium-based contrast agent.

Prognostic Significance of TMPRSS2-ERG Fusion Gene in Prostate Cancer.

Current research of prostate cancer (PCa) offers a promising way of identifying patients with adverse prognosis who do benefit from radical treatment that can affect quality of life as resections are associated with numerous side-effects. The aim of our study was to evaluate the relationship of TMPRSS2-ERG fusion gene status, tumor tissue prostate-specific antigen (PSA), prostate cancer antigen 3 (PCA3), miR-23b, miR-26a and miR-221 expression levels in combination with preoperative serum PSA level to the risk of PCa recurrence after radical prostatectomy. The study group consisted of 108 patients who underwent radical prostatectomy. PSA was measured in peripheral blood collected preoperativelly. The expression of TMPRSS2-ERG transcript and the expression of miR-23b, miR-26a and miR-221 in formalin-fixed, paraffin-embedded (FFPE) tumor tissues was analyzed by reverse transcription (RT) real-time polymerase chain reaction (PCR). Significantly shorter time to recurrence was observed in patients with high expression of TMPRSS2-ERG (p=0.0020). High levels of preoperative PSA (>10.0 ng/ml) proved to be marker of shorter time to recurrence (p=0.0153). The most promising marker of the risk of recurrence after radical prostatectomy was a combination of high level of preoperative serum PSA and high expression of TMPRSS2-ERG fusion transcript in tumor tissue (p=0.0001). A combination of high preoperative serum PSA and high expression of TMPRSS2-ERG could be promising in distinguishing those tumors that are aggressive and life-threatening.

Management of men with previous negative prostate biopsy.

Up to 70% of prostate biopsies are negative in men with suspected prostate cancer. Because of inherent limitations in biopsy strategies, a significant proportion of cancers are missed on initial biopsy. Following negative biopsy, men frequently exhibit persistently elevated prostate-specific antigen - raising concerns for missed diagnosis. We highlight the recent updates in the management of negative prostate biopsy. Advances in noninvasive diagnostics are available and assist clinicians in further substratifying risk of prostate cancer. Despite limited data, urinary prostate cancer antigen 3 and transmembrane protease serine 2 appear to have a promising predictive value for patients suspected of prostate cancer. The advent of multiparametricMRI allows the visualization of intermediate and high-grade prostate cancer, particularly in the troublesome anterior prostate. This modality may further provide the potential for magnetic resonance-guided targeted biopsies. Current data suggest that in the presence of suspicious radiological findings, magnetic resonance-guided biopsies have superior sensitivity profiles compared with traditional rebiopsy approaches. In the absence of multiparametricMRI or suspicious findings, traditional saturation biopsies are sufficient. The management of negative biopsies is evolving rapidly with emerging diagnostics to stratify risk of prostate cancer in men with previous negative biopsies. An increasing body of information supports the use of magnetic resonance-guided biopsies.

TCNQ-doped Cu-metal organic framework as a novel conductometric immunosensing platform for the quantification of prostate cancer antigen

Due to their hierarchical structures and high surface areas, several categories of metal organic frameworks (MOFs) have emerged as next-generation materials for a wide variety of applications, including sensors. However, the poor electrical conductivity is a bottleneck to exploit them in the development of electrochemical sensing devices. In this work, we for the first time report the development and application of tetracyanoquinodimethane (TCNQ)- doped thin films of copper-MOF, Cu3(BTC)2, assembled on gold screen printed electrodes, as an electrochemical sensing platform for highly sensitive detection of a prostate cancer marker. The structural and spectroscopic features of the synthesized material along with the morphological features of the prepared electrodes were characterized with diverse instrumental techniques. Doping the thin films of Cu3(BTC)2 with TCNQ improved the conductance of the base material by nine orders of magnitude (from 10−12 to 10−3S). This conducting platform was modified with antibodies to design an immunosensor for the prostate cancer antigen (PSA). The anti-PSA conjugated TCNQ- Cu3(BTC)2 provided PSA detection in a dynamic linear range of 0.1–100ng/mL to attain a limit of detection at 0.06ng/mL. The above sensor was specific to PSA even in the presence of other proteins. The practical utility of the immunosensor was also demonstrated against some spiked serum samples. The herein proposed TCNQ- Cu3(BTC)2 based detection system involves a robust physical immobilization of the antibodies to facilitate the detection of PSA over a broader and clinically significant concentration range.

Novel non-invasive urine-based gene expression assay discriminates between low- and high-risk prostate cancer before biopsy

Prostate-specific antigen (PSA)-based screening programs are controversial, and influential guideline panels have recommended against PSA screening in all men. A main limitation of PSA-based blood tests is the lack of a valid threshold to distinguish between a malignant and a benign condition. In addition, PSA screening generally fails to differentiate between low- and high-grade prostate cancer and thus, is not able to prevent patients from unnecessary biopsies. Alternative, urine-based tests have recently been developed and provide promising predictive accuracy regarding the aggressiveness of the disease. Two markers—prostate cancer antigen 3 (PCA3) and an androgen-related fusion protein (TMPRSS2-ERG)—were combined into a urine test several years ago. This Mi-Prostate Score (MiPS) significantly outperformed both PCA3 + PSA and PSA alone for the prediction of high-grade prostate cancer before biopsy. To date, these tests need pre-collection digital rectal examination to improve the predictive ability. Against this backdrop, a recent study presented a novel urine-based assay, using an exosome-derived gene expression signature. In a validation cohort of 519 patients, the area under receiver operating characteristic curve (AUC) showed superior predictive ability in the discrimination of Gleason scores ≥7 and <7 before biopsy, when compared to standard of care alone (0.73 vs. 0.63; P<0.001). Despite not showing better predictive accuracy than already existing urine-based tests, this novel exosome-derived assay allows pre-biopsy assessment without the need for digital rectal examination. Thus, any health professional can perform the test, which (I) spares the patient another digital rectal examination and (II) may facilitate clinical workflow.

The anti-tumour effect of a DNA vaccine carrying a fusion gene of human VEGFR2 and IL-12

ABSTRACTBecause of tumour dependence on angiogenesis, anti-angiogenic therapy has become the most attractive area of basic and clinical study in the field of cancer research. In order to create a synergistic effect on angiogenesis and immune regulation, we designed and constructed a new type of DNA vaccine that can express VEGFR2 (vascular endothelial growth factor receptor 2) and the prostate cancer antigen IL-12 (interleukin 12) in the same reading frame. The aim of this study was to investigate the anti-tumour activity of a eukaryotic expression plasmid carrying a fusion gene of human VEGFR2 and IL-12. According to the gene sequences in GenBank, we synthesized the human VEGFR2 and IL-12 genes. VEGFR2 and IL-12 were joined by a sequence encoding a Furin recognition site and a 2A cleavage site, and the resulting fusion gene was cloned into the eukaryotic expression vector pVAX1 to construct the expression plasmid pVAX1-VEGFR2-F2A-IL-12. The expression of VEGFR2 and IL-12 could be detected in 293T cells transfected with pVAX1-VEGFR2-F2A-IL-12 by enzyme-linked immunosorbent assay. Each of these proteins, and in particular co-expression of both proteins, can result in humoral and cellular immune responses in C57BL/6 mice. After injection into the tumour-bearing mouse model, the plasmid showed stronger inhibition of tumour growth than a plasmid expressing VEGFR2 alone. Our results demonstrate that a DNA vaccine carrying a fusion gene of human VEGFR2 and IL-12 could represent a promising approach for tumour immunotherapy.

Novel non-invasive urine-based gene expression assay discriminates between low- and high-risk prostate cancer before biopsy

: Prostate-specific antigen (PSA)-based screening programs are controversial, and influential guideline panels have recommended against PSA screening in all men. A main limitation of PSA-based blood tests is the lack of a valid threshold to distinguish between a malignant and a benign condition. In addition, PSA screening generally fails to differentiate between low- and high-grade prostate cancer and thus, is not able to prevent patients from unnecessary biopsies. Alternative, urine-based tests have recently been developed and provide promising predictive accuracy regarding the aggressiveness of the disease. Two markers—prostate cancer antigen 3 (PCA3) and an androgen-related fusion protein (TMPRSS2-ERG)—were combined into a urine test several years ago. This Mi-Prostate Score (MiPS) significantly outperformed both PCA3 + PSA and PSA alone for the prediction of high-grade prostate cancer before biopsy. To date, these tests need pre-collection digital rectal examination to improve the predictive ability. Against this backdrop, a recent study presented a novel urine-based assay, using an exosome-derived gene expression signature. In a validation cohort of 519 patients, the area under receiver operating characteristic curve (AUC) showed superior predictive ability in the discrimination of Gleason scores ≥7 and <7 before biopsy, when compared to standard of care alone (0.73 vs. 0.63; P<0.001). Despite not showing better predictive accuracy than already existing urine-based tests, this novel exosome-derived assay allows pre-biopsy assessment without the need for digital rectal examination. Thus, any health professional can perform the test, which (I) spares the patient another digital rectal examination and (II) may facilitate clinical workflow.