Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case–control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM.
Method
A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016.
Results
Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02–20.78) for mesothelin, 20.44 (95% CI 8.90–46.94) for calretinin, and 4.37 (95% CI 1.60–11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32–113.99), 17.89 (95% CI 3.93–81.49), and 2.77 (95% CI 0.47–16.21), respectively.
Conclusions
To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.
The fallopian tube has been implicated as a site of origin of sporadic and BRCA1-related ovarian cancer. To investigate if Ki-67 or p53 is altered in BRCA1 mutation carriers, we have studied the expression of these markers in morphologically normal mucosa in the fallopian tube and fimbriae.
Methods
Prophylactic adnexectomy specimens from 24 patients (eight BRCA1 mutation carriers, eight non-mutation carriers, and eight with unknown BRCA1 status), were scored by automated image analysis for the amount of Ki-67 and wild-type p53 expression. All patients had a history of breast cancer and a family history of breast or ovarian cancer.
Results
In the fimbriae, a median of 0.42 % Ki-67 and 0.04 % p53-positive epithelial cells was present, compared to a median of 0.36 % for Ki-67 and 0.05 % for p53 in the fallopian tube. Ki-67 expression decreased significantly with age (r = ?0.45, p = 0.028). In contrast, p53 expression was not age-dependent for the whole group of patients (r = 0.25, p = 0.25). Subgroup analysis revealed a difference for p53 expression of the BRCA1 mutation carriers with respect to age (median 0.039 vs. 0.082 % for age less or greater than 50.5 years). Consequently, the p53/Ki-67 ratio showed an age-dependent increase, which was accelerated in the BRCA1-positive patients.
Conclusions
Ki-67 and p53 expression varies in morphologically normal tubal epithelial cells depending on age and BRCA1 mutation status. This may reflect an altered and age-dependent DNA repair in BRCA1 mutation carriers and may be related to increased risk of ovarian cancer arising in the fallopian tube. 相似文献
Journal of Neurology - Moyamoya angiopathy (MMA) is a rare vasopathy, especially among European Caucasians. Data about demographics, clinical presentation, comorbid conditions, radiological... 相似文献
Round-window stimulation is a new clinical approach for the application of active middle-ear implants. To investigate factors influencing the efficiency of round-window stimulation, experiments in 6 human temporal bones were performed with different actuator geometries and coupling conditions. The experiments show that the amplitude ratio between stapes and round-window actuator vibration is most efficient when using a 1.0-mm diameter rod with a 30° inclined tip geometry and an attached silicone pad. In this case, the amplitude ratio is 0.34 for frequencies up to 1.5 kHz and 0.27 for frequencies up to 20 kHz, with a standard deviation of only 4-6 dB at most frequencies. The analysis of data presented here and in a companion paper suggests that control of proper round-window membrane pretension as well as the inclined tip geometry are the major requirements for maximal performance. 相似文献
In comparison to current on-market assays, the ARCHITECT rHTLV-I/II assay is the first fully automated assay that simultaneously detects human T-cell lymphotropic virus type I (HTLV-I) and type II (HTLV-II) in human serum and plasma. Specificity was assessed on 5646 blood donors and 692 clinical specimens. For sensitivity determination, 301 HTLV-I–positive and 105 HTLV-II–positive specimens were tested. Precision was between 3.98% and 4.31% coefficient of variation (CV) for specimens with 1 to 6 sample to cutoff. Specificity was 99.95% and 99.86% on specimens from blood donors and hospitalized patients, respectively. Sensitivity evaluation showed 100% detection on 301 HTLV-I and 105 HTLV-II specimens. HTLV-I and HTLV-II viruses are still circulating among general populations even in the low prevalence areas. To control the further spread of these retroviruses, we need to know that it is important to continue screening of blood. The performance evaluation data from this study demonstrate that the high throughput and fully automated ARCHITECT rHTLV-I/II chemiluminescence immunoassay effectively serves this purpose. 相似文献
Spinal and bulbar muscular atrophy (SBMA) is caused by an abnormal expansion of the CAG repeat in the androgen receptor gene. This study aimed to systematically phenotype a German SBMA cohort (n = 80) based on laboratory markers for neuromuscular, metabolic, and endocrine status, and thus provide a basis for the selection of biomarkers for future therapeutic trials.
Methods
We assessed a panel of 28 laboratory parameters. The clinical course and blood biomarkers were correlated with disease duration and CAG repeat length. A subset of 11 patients was evaluated with body fat MRI.
Results
Almost all patients reported muscle weakness (99%), followed by dysphagia (77%), tremor (76%), and gynecomastia (75%) as major complaints. Creatine kinase was the most consistently elevated (94%) serum marker, which, however, did not relate with either the disease duration or the CAG repeat length. Paresis duration and CAG repeat length correlated with dehydroepiandrosterone sulfate after correction for body mass index and age. The androgen insensitivity index was elevated in nearly half of the participants (48%).
Conclusions
Metabolic alterations in glucose homeostasis (diabetes) and fat metabolism (combined hyperlipidemia), and sex hormone abnormalities (androgen insensitivity) could be observed among SBMA patients without association with the neuromuscular phenotype. Dehydroepiandrosterone sulfate was the only biomarker that correlated strongly with both weakness duration and the CAG repeat length after adjusting for age and BMI, indicating its potential as a biomarker for both disease severity and duration and, therefore, its possible use as a reliable outcome measure in future therapeutic studies.