Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients

Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.     

Aminotransferases During Treatment Predict Long-Term Survival in Patients With Autoimmune Hepatitis Type 1: A Landmark Analysis

1. Download : Download high-res image (187KB)
2. Download : Download full-size image

     

Biochemical consequences of 5-fluorouracil gastrointestinal toxicity in rats; effect of high-dose uridine

Selective protection of the normal host tissues from the toxic effects of anticancer agents would allow the use of higher, probably more effective, doses of the drugs. It has been demonstrated that delayed high-dose uridine administration after 5-fluorouracil decreases the extent of myelosuppression and causes faster regeneration of the bone marrow. We studied the biochemical consequences of the gastrointestinal toxicity caused by 5-fluorouracil and the potential of high-dose uridine treatment to influence these adverse effects. 5-Fluorouracil caused dose-related decreases in the biochemical parameters (thymidine kinase, sucrase, maltase, alkaline phosphatase) selected as early markers of the impaired metabolic activity of the intestinal mucosa. The nadir of the biochemical changes was reached between 24 h and 72 h after 5-fluorouracil treatment, and complete regeneration of the mucosa took 6–7 days. Delayed high-dose uridine administration failed to mitigate the severity of the gastrointestinal damage that ensued after 5-fluorouracil treatment, but caused significantly earlier regeneration of the mucosa.     

Circular dichroism detection in high-performance liquid chromatography: Evaluation of the anisotropy factor

The application of a circular dichroism (c.d.) detection system in HPLC using a chiral stationary phase is presented. The simultaneous measurement of the absorbance and c.d. signal allows the evaluation of the anisotropy factor (g = Δ/) and thus the determination of the enantiomeric excess (e.e.) of the eluates. When this detection system is used in preparative chiral chromatography the collection of the enantiomeric fractions can be readily optimized.     

Determination of serotonin and 5-hydroxyindoleacetic acid in guinea pig and human prostate using HPLC

The finding of significant numbers of endocrine-paracrine (EP) cells in the prostate glands of guinea pigs and man suggests that these cells may be important in the regulation or modulation of prostatic function. Serotonin is a biogenic amine common to most prostatic EP cells. In order to extend current knowledge relating to these cells, an assay was developed using high-performance liquid chromatography to quantitate serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in guinea pig and human prostatic tissue extracts. Levels of serotonin and 5-HIAA in the guinea pig whole-gland preparation were 105.4 +/- 70.6 ng/g and 48.4 +/- 95.7 ng/g, respectively. Normal human prostatic tissue contained 1423.9 +/- 750.8 ng/g serotonin and 66.7 +/- 92.8 ng/g 5-HIAA. Recoveries ranged between 60 and 100%. The detection limits were 24 pg/injection for serotonin and 12 pg/injection for 5-HIAA. This assay provides an expeditious, specific and highly sensitive method for the simultaneous determination of monoamines in guinea pig and human prostatic tissue.     

关于生化自动分析仪噪音核查和反应限核查的几点讨论

生化自动分析仪在进行噪音核查和反应限核查之前，均已完成线性核查，已确定线性反应区，从吸光度-时间回归线计算出每分钟吸光度变化速度（△A／min）。在此基础上进行噪音核查（Noise Check）和反应限核查（Reaction Limit Check）。     

Pharmacokinetics of the 13C labeled anticancer agent temozolomide detected in vivo by selective cross-polarization transfer

The anticancer agent temozolomide labeled with ¹³C (8-Carbamoyl-3-13C-methylimidazo-[5,1-d]-1,2,3,5-tetrazin-4-(3H)-one), was noninvasively detected in subcutaneous RIF-1 tumors by a selective cross polarization ¹³C NMR method, at a field strength of 9.4T. Pharmacokinetics of the drug, at a dose of 150 mg/kg, were determined for intravenous and intraperitoneal modes of administration (three animals per mode). The half-life of the drug in the tumors was approximately 60 min. The uptake and clearance of the drug, however, varied significantly between individual hosts, for both modes of administration. These results demonstrate the feasibility of obtaining pharmacokinetics of anticancer agents for individual tumors without the need for a label that might modify drug activity (e.g., fluorine). The variability of the in vivo measurements, even within the same tumor model, demonstrates the necessity of directly monitoring the tumor to evaluate drug pharmacokinetics.     

HCV的检测方法

从发现丙型肝炎病毒以来 ,丙肝的检测技术发展迅速 ,灵敏度和特异性都有明显的提高 ,方法学在不断改进完善。笔者就近年来丙型肝炎的实验室检测方法作简要的综述     

The composite N1 component to gaps in noise.

OBJECTIVE: To indicate whether the double peaked N(1) to gaps in continuous white noise is a composite of onset and offset responses to transients or whether it reflects higher processing such as change or mismatch detection and to assess the role of attention in this process. METHODS: Evoked potentials were recorded to two binaural stimulus types: (1) gaps of different durations randomly distributed in continuous white noise; and (2) click pairs at intervals identical to those between gap onsets and offsets in the continuous noise stimulus. Potentials to these stimuli were recorded while subjects read a text and while detecting gaps in noise or click pairs. RESULTS: Potentials were detected to all click pairs and to gaps of 5 ms or longer, corresponding to the subjects' psychoacoustic gap detection threshold. With long gap durations of 200-800 ms, distinct potentials to gap onset and gap offset were observed. The waveforms to all click pairs and to offsets of long gaps were similar and single-peaked, while potentials to gaps of 10 ms and longer, and potentials to onsets of long gaps were double-peaked, consisting of two N(1) negativities, 60 ms apart, irrespective of gap duration. The first (N(1a)), was more frontal in its distribution and similar to that of clicks. The second (N(1b)) peak's distribution was more central/temporal and its source locations and time course of activity were distinct. No effects of attention on any of the varieties and constituents of N(1) were observed. CONCLUSIONS: Comparing potentials to gap onsets, to click pairs and to gap offsets, suggests that potentials to gap onsets involve not only sound onset/offset responses (N(1), N(1a)) but also the subsequent pre-attentive perception of the cessation of an ongoing sound (N(1b)). We propose that N(1b) is distinct from change or mismatch detection and is associated with termination of an ongoing continuous stimulus. We propose to call it the N(egation)-process. SIGNIFICANCE: A constituent of the N(1) complex is shown to be associated with the pre-attentive perception of termination of an ongoing stimulus and to have distinct scalp distribution and intracranial sources.