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Molecular insights into substrate specificity of prostate specific antigen through structural modeling

Prostate Specific Antigen's (PSA) role as a biomarker for prostate cancer is well established but the physiological role of its serine protease activity in the pathobiology of normal prostate and prostate carcinogenesis remains largely unknown. In light of recent studies that implicate PSA's enzymatic activity in the initiation and/or progression of prostate cancer, we performed a molecular modeli

Pretreatment prostate-specific antigen (PSA) velocity and doubling time are associated with outcome but neither improves prediction of outcome beyond pretreatment PSA alone in patients treated with radical prostatectomy

Purpose: Controversy exists as to whether current pretreatment prostate-specific antigen (PSA) dynamics enhance outcome prediction in patients undergoing treatment for prostate cancer. We assessed whether pretreatment PSA velocity (PSAV) or doubling time (PSADT) predicted outcome in men undergoing radical prostatectomy and whether any definition enhanced accuracy of an outcome prediction model. Pa

NF-κB regulates androgen receptor expression and prostate cancer growth

Prostate cancers that progress during androgen-deprivation therapy often overexpress the androgen receptor (AR) and depend on AR signaling for growth. In most cases, increased AR expression occurs without gene amplification and may be due to altered transcriptional regulation. The transcription factor nuclear factor (NF)-κB, which is implicated in tumorigenesis, functions as an important downstrea

Early prostate-specific antigen changes and the diagnosis and prognosis of prostate cancer

PURPOSE OF REVIEW: To delineate how recent findings on prostate-specific antigen (PSA) can improve prediction of risk, detection, and prediction of clinical endpoints of prostate cancer (PCa). RECENT FINDINGS: The widely used PSA cut-point of 4.0 ng/ml increasingly appears arbitrary, but no cut-point achieves both high sensitivity and high specificity. The accuracy of detecting PCa can be increase

Circulating prostate tumor cells detected by Reverse transcription-PCR in men with localized or castration-refractory prostate cancer : Concordance with CellSearch assay and association with bone metastases and with survival

Reverse transcription-PCR (RT-PCR) assays have been used for analysis of circulating tumor cells (CTCs), but their clinical value has yet to be established. We assessed men with localized prostate cancer or castration-refractory prostate cancer (CRPC) for CTCs via real-time RT-PCR assays for KLK3 [kallikrein-related peptidase 3; i.e., prostate-specific antigen (PSA)] and KLK2 mRNAs. We also assess

Fluorescence in situ hybridization analysis of circulating tumor cells in metastatic prostate cancer

Purpose: To assess the feasibility of characterizing gene copy number alteration by fluorescence in situ hybridization (FISH) of circulating tumor cells (CTC) isolated using the Cell Search system in patients with progressive castration-resistant metastatic prostate cancer. Experimental Design: We used probe combinations that included the androgen receptor (AR)and MYC genes for FISH analysis of CT

Systematic review of Pretreatment prostate-specific antigen velocity and doubling time as predictors for prostate cancer

Purpose Pretreatment prostate-specific antigen (PSA) dynamics (PSA velocity and PSA doubling time) are widely advocated as useful prognostic markers in prostate cancer. We aimed to assess the published evidence for the clinical utility of PSA dynamics in this population. Methods We conducted a systematic review of studies published before March 2007 in which a PSA dynamic (velocity or doubling tim

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers

BACKGROUND: Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. METHODS: Published reports relevant to use of tumor markers for 5 cancer sites - testicular, prostate, colorectal, breast, and ovarian - were critically reviewed. RESULTS: For testicular cancer, α-fetoprotein, human chorionic g

Systematic review of statistical methods used in molecular marker studies in cancer

BACKGROUND. There is wide interest in the use of molecular markers for the early detection of cancer, the prediction of disease outcome, and the selection of patients for chemotherapy. Despite significant and increasing research activity, to the authors' knowledge only a small number of molecular markers have been successfully integrated into clinical practice. In the current study, the experiment

Serum Markers for Prostate Cancer : A Rational Approach to the Literature

Introduction: Due to its universal applicability for early detection and prediction of cancer stage and disease recurrence, widespread implementation of serum-based prostate-specific antigen (PSA) measurements has a significant influence on current treatment strategies for men with prostate cancer (PCa). However, over-detection and the resultant over-treatment of indolent cancers have been strongl

Expression of Prostate Specific Antigen on the Surface of a Filamentous Phage

We have constructed two phagemid vectors containing the gene coding for human Prostate Specific Antigen (PSA) translationally fused to a pelB signal sequence and minor coat protein III of phage fd leading to phage particles that carry PSA on their tips. Phages were characterized by Western blotting and by panning, using biotinylated monoclonal anti-PSA antibodies immobilized onto streptavidin-coat

Complex formation between protein C inhibitor and prostate‐specific antigen in vitro and in human semen

Protein C inhibitor (PCI), a serine‐proteinase inhibitor first purified from human blood plasma, occurs at high concentrations (3–4 μM) in seminal fluid in both a high‐molecular‐mass and low‐molecular‐mass form. Immunochemical data have previously suggested that PCI in seminal plasma forms complexes with the most abundant serine proteinase in semen, prostate‐specific antigen (PSA). To provide a st

Can RE Help Better Prepare Industrial AI for Commercial Scale?

This issue marks the start of my term as department editor for the “Requirements” column. I very much look forward to exploring contemporary aspects of requirements and requirements engineering (RE) in the coming years! As an institute researcher with RISE, I primarily work in strictly regulated domains, in which requirements are cornerstones in the development activities. Please check my introduc

Prostate specific antigen predominantly forms a complex with alpha1‐antichymotrypsin in blood. Implications for procedures to measure prostate specific antigen in serum

Background. Prostate specific antigen (PSA) is a zymogen of a 33‐kilodalton (kD) serine proteinase with extensive similarity to glandular kallikreins. The mechanism responsible for converting the zymogen into active proteinase has not been defined, but active PSA may be irreversibly inactivated in vitro by two of the major proteinase inhibitors in blood: alpha1‐antichymotrypsin and alpha2‐macroglo

Molecular cloning and sequence analysis of the cDNA encoding the human acrosin-trypsin inhibitor (HUSI-II)

A complete cDNA clone encoding the human acrosin-trypsin inhibitor HUSI-II has been isolated from a cDNA library of human testis and completely sequenced. The cDNA of 594 bp contained an open reading frame of 252 base pairs, The deduced amino acid sequence comprised the complete amino acid sequence of HUSI-II[1] and a putative signal peptide. Northern blotting analysis revealed that HUSI-II is syn

Gastricsin‐Mediated Proteolytic Degradation of Human Seminal Fluid Proteins at pH Levels Found in the Human Vagina

The proteolytic degradation of human seminal fluid proteins at acidic conditions has been investigated. Upon acidification to the pH level of the human vagina, autoproteolysis of most seminal fluid proteins occurred after 30 minute of incubation at 37°C. The degradation was unaffected by inhibitors of serine, thiol, or me‐tallo proteases, whereas pepstatin prevented any proteolysis. The proteins i

Structure, function, and regulation of the enzyme activity of prostate-specific antigen

Prostate-specific antigen (PSA) and human glandular kallikrein 1 (hGK-1) are structurally similar products of the human glandular kallikrein gene locus on chromosome 19 that become selectively expressed by human prostate tissue. PSA is one of the most abundant prostate-derived proteins in the seminal fluid. The mature form of PSA, a single-chain glycoprotein of 237 amino acids, is a serine proteas