scholarly journals A Caenorhabditis elegans behavioral assay distinguishes early stage prostate cancer patient urine from controls

Biology Open ◽  
2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Morgan Thompson ◽  
Noemi Sarabia Feria ◽  
Ally Yoshioka ◽  
Eugene Tu ◽  
Fehmi Civitci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Caenorhabditis Elegans ◽  
Early Stage ◽  
False Positive Rate ◽  
Specific Antigen ◽  
Dependent Manner ◽  
C Elegans ◽  
Non Invasive ◽  
Volatile Organic ◽  
Positive Rate

ABSTRACT Current methods for non-invasive prostate cancer (PrCa) detection have a high false-positive rate and often result in unnecessary biopsies. Previous work has suggested that urinary volatile organic compound (VOC) biomarkers may be able to distinguish PrCa cases from benign disease. The behavior of the nematode Caenorhabditis elegans has been proposed as a tool to take advantage of these potential VOC profiles. To test the ability of C. elegans Bristol N2 to distinguish PrCa cases from controls, we performed chemotaxis assays using human urine samples collected from men screened for PrCa. Behavioral response of nematodes towards diluted urine from PrCa cases was compared to response to samples from cancer-free controls. Overall, we observed a significant attraction of young adult-stage C. elegans nematodes to 1:100 diluted urine from confirmed PrCa cases and repulsion of C. elegans to urine from controls. When C. elegans chemotaxis index was considered alongside prostate-specific antigen levels for distinguishing cancer from cancer-free controls, the accuracy of patient classification was 81%. We also observed behavioral attraction of C. elegans to two previously reported VOCs to be increased in PrCa patient urine. We conclude nematode behavior distinguishes PrCa case urine from controls in a dilution-dependent manner.

Is one narrative enough? Analytical tools should match the problems they address

2020 ◽  
pp. medethics-2020-106309
Author(s):  
Nathan Hodson ◽  
Susan Bewley
Keyword(s):  
Prostate Cancer ◽  
False Positive Rate ◽  
Specific Antigen ◽  
Narrative Ethics ◽  
Psa Screening ◽  
The Status ◽  
Positive Rate ◽  
Meta Analyses ◽  
Analytical Tools ◽  
Asymptomatic Men

Jeff Nisker describes his personal experience of a diagnosis of advanced prostate cancer and the kindnesses he received from friendly doctors. He claims that this narrative account supports the promotion of Prostate Specific Antigen (PSA) screening for asymptomatic men and impugns statisticians, mistakenly thinking that their opposition to PSA screening derives from concerns about financial cost. The account inadvertently demonstrates the danger of over-reliance on a single ethical tool for critical analysis. In the first part of this response, we describe the statistical evidence. The most reliable Cochrane meta-analyses have not shown that PSA screening saves lives overall. Moreover, the high false positive rate of PSA screening leads to overinvestigation which results in unnecessary anxiety and increased cases of unnecessary sepsis, urinary incontinence and sexual dysfunction. Then we describe how narrative ethics alone is an insufficient tool to make claims about policies, such as PSA screening, which have hidden harms. Although Nisker’s story-telling is compelling and evokes emotions, narrative ethics of this sort have an inherent bias against people who would be harmed by the counterfactual. Particular care must be taken to look for and consider those untellable stories. Ethicists who only consider narratives which are readily at hand risk harming those who are voiceless or protected by the status quo. PSA screening is the wrong tool to reduce prostate cancer deaths and narrative ethics is the wrong tool to appraise this policy. It is vital that the correct theoretical tools are applied to the medical and ethical questions under scrutiny.

Prostate-Specific Antigen in Prostate Cancer

1986 ◽  
Vol 1 (2) ◽  
pp. 67-76 ◽  
Author(s):  
Manabu Kuriyama
Keyword(s):  
Prostate Cancer ◽  
Tumor Marker ◽  
Cancer Patients ◽  
Prostate Specific Antigen ◽  
False Positive Rate ◽  
Specific Antigen ◽  
Benign Prostatic Hypertrophy ◽  
High Sensitivity ◽  
Positive Rate ◽  
Normal Controls

Prostate-specific antigen (PA) has been evaluated clinically as a tumor marker of prostate cancer with the use of enzyme immunoassay (EIA). For serodetection of prostate cancer, PA was assayed in a total of 1,109 sera. From mean ± 3 S.D. of normal controls, upper cut-off values in males were decided as 2.5 and 1.2 ng/ml in Americans and Japanese, respectively. Serum PA values in prostate cancer patients were positive in 78% of Americans and 62% of Japanese. However, in benign prostatic hypertrophy (BPH) cases, a high false positive rate of 41% was observed in Americans. Simultaneous assays of serum PA and PAP showed high sensitivity and specificity in the detection of prostate cancer. This antigen could be used, as well as PAP, for monitoring prostate cancer patients. Furthermore, serum PA levels prior to treatment may express to some degree the malignant potential of the cancer. These results suggest that PA may be useful as a tumor marker of prostate cancer.

scholarly journals Genome-wide cell-free DNA methylation analyses improve accuracy of non-invasive diagnostic imaging for early-stage breast cancer

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiaqi Liu ◽  
Hengqiang Zhao ◽  
Yukuan Huang ◽  
Shouping Xu ◽  
Yan Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Diagnostic Imaging ◽  
Early Stage ◽  
False Positive Rate ◽  
Whole Genome ◽  
Non Invasive ◽  
Free Dna ◽  
Positive Rate

AbstractEarly detection is crucial to improve breast cancer (BC) patients’ outcomes and survival. Mammogram and ultrasound adopting the Breast Imaging Reporting and Data System (BI-RADS) categorization are widely used for BC early detection, while suffering high false-positive rate leading to unnecessary biopsy, especially in BI-RADS category-4 patients. Plasma cell-free DNA (cfDNA) carrying on DNA methylation information has emerged as a non-invasive approach for cancer detection. Here we present a prospective multi-center study with whole-genome bisulfite sequencing data to address the clinical utility of cfDNA methylation markers from 203 female patients with breast lesions suspected for malignancy. The cfDNA is enriched with hypo-methylated genomic regions. A practical computational framework was devised to excavate optimal cfDNA-rich DNA methylation markers, which significantly improved the early diagnosis of BI-RADS category-4 patients (AUC from 0.78–0.79 to 0.93–0.94). As a proof-of-concept study, we performed the first blood-based whole-genome DNA methylation study for detecting early-stage breast cancer from benign tumors at single-base resolution, which suggests that combining the liquid biopsy with the traditional diagnostic imaging can improve the current clinical practice, by reducing the false-positive rate and avoiding unnecessary harms.

Prostate Cancer: Biology, Incidence, Detection Methods, Treatment Methods, and Vaccines

2020 ◽  
Vol 20 (10) ◽  
pp. 847-854
Author(s):  
Ronald Bartzatt
Keyword(s):  
Prostate Cancer ◽  
Cancer Treatment ◽  
Prostate Specific Antigen ◽  
Cancer Biology ◽  
Early Stage ◽  
Specific Antigen ◽  
Detection Methods ◽  
Hormone Refractory Prostate Cancer ◽  
High Risk Prostate Cancer ◽  
Hormone Refractory

Cancer of the prostate are cancers in which most incidences are slow-growing, and in the U.S., a record of 1.2 million new cases of prostate cancer occurred in 2018. The rates of this type of cancer have been increasing in developing nations. The risk factors for prostate cancer include age, family history, and obesity. It is believed that the rate of prostate cancer is correlated with the Western diet. Various advances in methods of radiotherapy have contributed to lowering morbidity. Therapy for hormone- refractory prostate cancer is making progress, for almost all men with metastases will proceed to hormone-refractory prostate cancer. Smoking cigarettes along with the presence of prostate cancer has been shown to cause a higher risk of mortality in prostate cancer. The serious outcome of incontinence and erectile dysfunction result from the cancer treatment of surgery and radiation, particularly for prostate- specific antigen detected cancers that will not cause morbidity or mortality. Families of patients, as well as patients, are profoundly affected following the diagnosis of prostate cancer. Poor communication between spouses during prostate cancer increases the risk for poor adjustment to prostate cancer. The use of serum prostate-specific antigen to screen for prostate cancer has led to a greater detection, in its early stage, of this cancer. Prostate cancer is the most common malignancy in American men, accounting for more than 29% of all diagnosed cancers and about 13% of all cancer deaths. A shortened course of hormonal therapy with docetaxel following radical prostatectomy (or radiation therapy) for high-risk prostate cancer has been shown to be both safe and feasible. Patients treated with docetaxel-estramustine had a prostate-specific antigen response decline of at least 50%. Cancer vaccines are an immune-based cancer treatment that may provide the promise of a non-toxic but efficacious therapeutic alternative for cancer patients. Further studies will elucidate improved methods of detection and treatment.

A Cuticle Collagen Encoded by the lon-3 Gene May Be a Target of TGF-β Signaling in Determining Caenorhabditis elegans Body Shape

Genetics ◽  
2002 ◽  
Vol 162 (4) ◽  
pp. 1631-1639
Author(s):  
Yo Suzuki ◽  
Gail A Morris ◽  
Min Han ◽  
William B Wood
Keyword(s):  
Caenorhabditis Elegans ◽  
Body Shape ◽  
Small Body ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Cellular Mechanisms ◽  
C Elegans ◽  
Gene Expression Analyses ◽  
Dose Dependent

Abstract The signaling pathway initiated by the TGF-β family member DBL-1 in Caenorhabditis elegans controls body shape in a dose-dependent manner. Loss-of-function (lf) mutations in the dbl-1 gene cause a short, small body (Sma phenotype), whereas overexpression of dbl-1 causes a long body (Lon phenotype). To understand the cellular mechanisms underlying these phenotypes, we have isolated suppressors of the Sma phenotype resulting from a dbl-1(lf) mutation. Two of these suppressors are mutations in the lon-3 gene, of which four additional alleles are known. We show that lon-3 encodes a collagen that is a component of the C. elegans cuticle. Genetic and reporter-gene expression analyses suggest that lon-3 is involved in determination of body shape and is post-transcriptionally regulated by the dbl-1 pathway. These results support the possibility that TGF-β signaling controls C. elegans body shape by regulating cuticle composition.

scholarly journals Prostate Cancer Liquid Biopsy Biomarkers’ Clinical Utility in Diagnosis and Prognosis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3373
Author(s):  
Milena Matuszczak ◽  
Jack A. Schalken ◽  
Maciej Salagierski
Keyword(s):  
Prostate Cancer ◽  
Liquid Biopsy ◽  
Current Knowledge ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Digital Rectal Examination ◽  
Cost Effective ◽  
Non Invasive ◽  
Diagnosis And Prognosis

Prostate cancer (PCa) is the most common cancer in men worldwide. The current gold standard for diagnosing PCa relies on a transrectal ultrasound-guided systematic core needle biopsy indicated after detection changes in a digital rectal examination (DRE) and elevated prostate-specific antigen (PSA) level in the blood serum. PSA is a marker produced by prostate cells, not just cancer cells. Therefore, an elevated PSA level may be associated with other symptoms such as benign prostatic hyperplasia or inflammation of the prostate gland. Due to this marker’s low specificity, a common problem is overdiagnosis, which leads to unnecessary biopsies and overtreatment. This is associated with various treatment complications (such as bleeding or infection) and generates unnecessary costs. Therefore, there is no doubt that the improvement of the current procedure by applying effective, sensitive and specific markers is an urgent need. Several non-invasive, cost-effective, high-accuracy liquid biopsy diagnostic biomarkers such as Progensa PCA3, MyProstateScore ExoDx, SelectMDx, PHI, 4K, Stockholm3 and ConfirmMDx have been developed in recent years. This article compares current knowledge about them and their potential application in clinical practice.

scholarly journals Role of Testosterone Levels on the Combinatorial Effect of Boswellia serrata Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells

2021 ◽  
Vol 20 ◽  
pp. 153473542199682
Author(s):  
Prathesha Pillai ◽  
Ginil Kumar Pooleri ◽  
Shantikumar V. Nair
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Early Stage ◽  
Therapeutic Option ◽  
Specific Antigen ◽  
Cell Killing ◽  
Receptor Expression ◽  
Lncap Cells ◽  
Boswellia Serrata ◽  
Physiological Serum

Co-therapy with herbal extracts along with current clinical drugs is being increasingly recognized as a useful complementary treatment for cancer. The anti-cancer property of the phyto-derivative acetyl-11 keto β boswellic acid (AKBA) has been studied in many cancers, including prostate cancer. However, the whole extract of the gum resin Boswellia serrata (BS) and anti-androgen enzalutamide has not been explored in prostate cancer to date. We hypothesized that the BS extract containing 30% (AKBA) with enzalutamide acted synergistically in the early phase of cancer, especially in LNCaP cells, by inhibiting androgen receptor (AR) and by reducing cell proliferation, and further, that the extract would be superior to the action of the active ingredient AKBA when used alone or in combination with enzalutamide. To test our hypothesis, we treated LNCaP cells with BS extract or AKBA and enzalutamide both individually and in combination to analyze cell viability under different levels of dihydrotestosterone (DHT). The inhibition of androgen receptor (AR) followed by the expression of prostate-specific antigen (PSA) and the efflux mechanism of the cells were analyzed to determine the effect of the combination on the cellular mechanism. Cells derived from prostate cancer patients were also tested with the combination. Only 6 µM enzalutamide along with BS in the range of 4.1 µg/ml to 16.4 µg/ml gave the best synergistic results with nearly 50% cell killing even though standard enzalutamide doses were as high as 48 µM. Cell killing was most effective at intermediate DHT concentrations of approximately 1 nM, which corresponds to normal physiological serum levels of DHT. The Pgp expression level and the androgen receptor expression levels were reduced under the combination treatment; the former helping to minimize drug efflux and the latter by reducing the sensitivity to hormonal changes. Furthermore, the combination reduced the PSA level secreted by the cells. In contrast, AKBA could not achieve the needed synergism for adequate cell killing at equivalent concentrations. The combination of enzalutamide and BS extract containing 30% AKBA because of their synergistic interaction is an attractive therapeutic option for treating early stage (hormone-dependent) prostate cancer and is superior to the use of AKBA alone.

scholarly journals Biofluid quantification of TWEAK/Fn14 axis in combination with a selected biomarker panel improves assessment of prostate cancer aggressiveness

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Xavier Ruiz-Plazas ◽  
Esther Rodríguez-Gallego ◽  
Marta Alves ◽  
Antonio Altuna-Coy ◽  
Javier Lozano-Bartolomé ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Biochemistry ◽  
Specific Antigen ◽  
Total Serum ◽  
Mrna Levels ◽  
Biomarker Panel ◽  
Non Invasive ◽  
Clinical Biomarkers ◽  
Cancer Aggressiveness ◽  
Aggressive Tumors

Abstract Background Conventional clinical biomarkers cannot accurately differentiate indolent from aggressive prostate cancer (PCa). We investigated the usefulness of a biomarker panel measured exclusively in biofluids for assessment of PCa aggressiveness. Methods We collected biofluid samples (plasma/serum/semen/post-prostatic massage urine) from 98 patients that had undergone radical prostatectomy. Clinical biochemistry was performed and several cytokines/chemokines including soluble(s) TWEAK, sFn14, sCD163, sCXCL5 and sCCL7 were quantified by ELISA in selected biofluids. Also, the expression of KLK2, KLK3, Fn14, CD163, CXCR2 and CCR3 was quantified by real-time PCR in semen cell sediment. Univariate, logistic regression, and receiver operating characteristic (ROC) analyses were used to assess the predictive ability of the selected biomarker panel in conjunction with clinical and metabolic variables for the evaluation of PCa aggressiveness. Results Total serum levels of prostate-specific antigen (PSA), semen levels of sTWEAK, fasting glycemia and mRNA levels of Fn14, KLK2, CXCR2 and CCR3 in semen cell sediment constituted a panel of markers that was significantly different between patients with less aggressive tumors [International Society of Urological Pathology (ISUP) grade I and II] and those with more aggressive tumors (ISUP grade III, IV and V). ROC curve analysis showed that this panel could be used to correctly classify tumor aggressiveness in 90.9% of patients. Area under the curve (AUC) analysis revealed that this combination was more accurate [AUC = 0.913 95% confidence interval (CI) 0.782–1] than a classical non-invasive selected clinical panel comprising age, tumor clinical stage (T-classification) and total serum PSA (AUC = 0.721 95% CI 0.613–0.830). Conclusions TWEAK/Fn14 axis in combination with a selected non-invasive biomarker panel, including conventional clinical biochemistry, can improve the predictive power of serum PSA levels and could be used to classify PCa aggressiveness.

scholarly journals Dynamic Contrast-Enhanced Imaging as a Prognostic Tool in Early Diagnosis of Prostate Cancer: Correlation with PSA and Clinical Stage

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Xingchen Wu ◽  
Petri Reinikainen ◽  
Mika Kapanen ◽  
Tuula Vierikko ◽  
Pertti Ryymin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factors ◽  
Early Diagnosis ◽  
Early Stage ◽  
Clinical Stage ◽  
Specific Antigen ◽  
Transfer Constant ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced

Background and Purpose. Although several methods have been developed to predict the outcome of patients with prostate cancer, early diagnosis of individual patient remains challenging. The aim of the present study was to correlate tumor perfusion parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinical prognostic factors and further to explore the diagnostic value of DCE-MRI parameters in early stage prostate cancer. Patients and Methods. Sixty-two newly diagnosed patients with histologically proven prostate adenocarcinoma were enrolled in our prospective study. Transrectal ultrasound-guided biopsy (12 cores, 6 on each lobe) was performed in each patient. Pathology was reviewed and graded according to the Gleason system. DCE-MRI was performed and analyzed using a two-compartmental model; quantitative parameters including volume transfer constant (Ktrans), reflux constant (Kep), and initial area under curve (iAUC) were calculated from the tumors and correlated with prostate-specific antigen (PSA), Gleason score, and clinical stage. Results. Ktrans (0.11 ± 0.02 min−1 versus 0.16 ± 0.06 min−1; p<0.05), Kep (0.38 ± 0.08 min−1 versus 0.60 ± 0.23 min−1; p<0.01), and iAUC (14.33 ± 2.66 mmoL/L/min versus 17.40 ± 5.97 mmoL/L/min; p<0.05) were all lower in the clinical stage T1c tumors (tumor number, n=11) than that of tumors in clinical stage T2 (n=58). Serum PSA correlated with both tumor Ktrans (r=0.304, p<0.05) and iAUC (r=0.258, p<0.05). Conclusions. Our study has confirmed that DCE-MRI is a promising biomarker that reflects the microcirculation of prostate cancer. DCE-MRI in combination with clinical prognostic factors may provide an effective new tool for the basis of early diagnosis and treatment decisions.

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