Detection Of Early Stage Prostate Cancer Research Articles

PSMA1-mediated ultrasmall gold nanoparticles facilitate tumor targeting and MR/CT/NIRF multimodal detection of early-stage prostate cancer

Prostate-specific membrane antigen (PSMA) is a prominent biomarker for prostate cancer (PCa) diagnosis. Safe contrast agents able to render the expression and distribution of PSMA would facilitate early accurate screening and prognostic prediction of PCa. However, current Gd-containing nanoparticles are often limited by nonspecific redistribution in mononuclear phagocyte system (MPS) and inadequate perfusion to target sites. Besides, intrinsic defects of magnetic resonance (MR) equipment also hamper their use for precisely depicting PSMA details. Herein, we devised a novel noninvasive MR/CT/NIRF multimodal contrast agent (AGGP) coordinated to a high-affinity PSMA ligand (PSMA1) to specifically detect and quantify PSMA expression in PCa lesions, which exhibited formidable tripe-modal signal augments, preferential PSMA targeting, effective MPS escaping and profitable renal-clearable behavior in living mice. Biocompatibility and histopathological studies substantiated high security of AGGP in vivo, opening the door to future opportunities for improving early-stage PCa detection and clinical implementation of more effective multifunctional nanotherapeutics.

Memristive biosensors based on full-size antibodies and antibody fragments

For the first time memristive biosensors developed by the incorporation of scAbs (single-chain antibody fragments) enabling label-free detection of free Prostate Specific Antigen (fPSA) for early-stage detection of prostate cancer (PC) are reported. In addition, the first ever-published report of a direct relationship between the size of the bio-probes used to transfer specificity to the sensor and the voltage gap is here included. The proposed bio-detection is achieved by means of a voltage gap acquired in the electrical response of memristive sensors obtained by the bio-modification of silicon nanowire arrays. A comparison between memristive biosensors based on full-size antibodies and antibody fragments is also demonstrated by analysis of the surface morphology via Scanning Electron Microscopy. This new kind of biosensors provide excellent analytical sensitivity with a limit-of-detection down to 0.144 pg/mL on PSA.

An Ultra-Rapid Biosensory Point-of-Care (POC) Assay for Prostate-Specific Antigen (PSA) Detection in Human Serum.

Prostate-specific antigen (PSA) is the established routine screening tool for the detection of early-stage prostate cancer. Given the laboratory-centric nature of the process, the development of a portable, ultra rapid high-throughput system for PSA screening is highly desirable. In this study, an advancedpoint-of-care system for PSA detection in human serum was developed based on a cellular biosensor where the cell membrane was modified by electroinserting a specific antibody against PSA. Thirty nine human serum samples were used for validation of this biosensory system for PSA detection. Samples were analyzed in parallel with a standard immunoradiometric assay (IRMA) and an established electrochemical immunoassay was used for comparison purposes. They were classified in three different PSA concentration ranges (0, <4 and ≥4 ng/mL). Cells membrane-engineered with 0.25 μg/mL anti-PSA antibody demonstrated a statistically lower response against the upper (≥4 ng/mL) PSA concentration range. In addition, the cell-based biosensor performed better than the immunosensor in terms of sensitivity and resolution against positive samples containing <4 ng/mL PSA. In spite of its preliminary, proof-of-concept stage of development, the cell-based biosensor could be used as aninitiative for the development of a fast, low-cost, and high-throughput POC screening system for PSA.

Emerging Roles of Human Prostatic Acid Phosphatase

Prostate cancer is one of the most prevalent non-skin related cancers. It is the second leading cause of cancer deaths among males in most Western countries. If prostate cancer is diagnosed in its early stages, there is a higher probability that it will be completely cured. Prostatic acid phosphatase (PAP) is a non-specific phosphomonoesterase synthesized in prostate epithelial cells and its level proportionally increases with prostate cancer progression. PAP was the biochemical diagnostic mainstay for prostate cancer until the introduction of prostate-specific antigen (PSA) which improved the detection of early-stage prostate cancer and largely displaced PAP. Recently, however, there is a renewed interest in PAP because of its usefulness in prognosticating intermediate to high-risk prostate cancers and its success in the immunotherapy of prostate cancer. Although PAP is believed to be a key regulator of prostate cell growth, its exact role in normal prostate as well as detailed molecular mechanism of PAP regulation is still unclear. Here, many different aspects of PAP in prostate cancer are revisited and its emerging roles in other environment are discussed.

Individualized Decision-Making for Older Men With Prostate Cancer: Balancing Cancer Control With Treatment Consequences Across the Clinical Spectrum

Prostate cancer (PCa) is the most prevalent non-skin cancer among men and is the second leading cause of cancer death in men. PCa has an increased incidence and prevalence in older men. Age-associated incidence is on the rise due to increased screening in the older population. This has led to a sharp rise in the detection of early stage PCa. Given the indolent nature of many prostatic malignancies, a large proportion of older men with PCa will ultimately die from other causes. As a result, physicians and patients are faced with the challenge of identifying optimal treatment strategies for localized PCa, biochemically recurrent PCa and later-stage PCa. Age-related changes can impact tolerance of hormonal therapy and chemotherapy in men with metastatic disease and shift the risk-benefit ratio of these treatments. Tools such as the Comprehensive Geriatric Assessment (CGA) can help estimate remaining life expectancy and can help predict treatment-related morbidity and mortality in older men. Application of CGA in older men with PCa is important to help individualize and optimize treatment strategies. Research that integrates multidisciplinary and multidimensional assessment of PCa and the patient's overall health status is needed.

Mass Screening of Prostate Cancer and its Impact on Inhabitants in Akita Prefecture, Japan

In 2001, the Akita Medical Association started a prostate cancer (PC) mass screening project for >or= 50-year-old male inhabitants in individual municipalities of Akita Prefecture, utilizing serum prostate-specific antigen. The number of examinees increased from 4321 in 2001 to 29,936 in 2006, while the annual rate of examinees per target inhabitants remained at 11.6 to 16.8% and the fraction of repeat examinees increased up to 77% in 2006. A total of 944 PCs were screened with a stage B tumor incidence of 84.1% (range: 82.2 to 86.6%). The annual PC detection rate was 0.95 to 1.11% for the first 4 years, but then declined to 0.54% in 2006 mainly due to the increase of repeat examinees. PSA mass screening is effective for the detection of early stage PC, but a further promotion is needed to mobilize the sleeping inhabitants. Indeed, the number of new PC patients in 17 major hospitals in Akita Prefecture rapidly increased after the mass screening started (3.2-fold), suggesting an enlightenment effect of the screening project on both the inhabitants and general physicians.

Intracrinology: The Basis for the Rational Design of Endocrine Therapy at All Stages of Prostate Cancer

Adrenal androgens contribute 40% of total androgens in adult men. The inactive precursor steroids dehydroepiandrosterone (DHEA) and DHEA-sulfate are secreted in large amounts by the adrenals and reach the prostate and other peripheral target tissues, where they are transformed into the potent androgen dihydrotestosterone (DHT). We have cloned and sequenced the cDNAs and/or genes which encode the enzymes responsible for the transformation of DHEA into DHT, namely 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase, 17 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase. Blockade of DHT synthesized by these enzymes, with a pure antiandrogen of the class of flutamide, prolongs life in advanced prostate cancer, the effect being much more important when a small number of metastases is present. Most importantly, 3-month combination therapy reduces cancer-positive margins at radical prostatectomy, from 38.5% in control patients to only 13% in those who received combination therapy. Combined with an efficient strategy for detection of early-stage prostate cancer, the present approach could offer the possibility of a cure to more than 80% of prostate cancer patients, compared with the present situation where a cure can be offered to less than 20% of patients, since the first diagnosis of prostate cancer is usually made at a late stage of the disease.