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Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration's (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31-35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was approximately 93% (PRNT50) and approximately 54% (PRNT90). Sera with high SARS-CoV-2 antibody levels (>960 enzyme-linked immunosorbent assay titers) showed maximal activity, but not all high-titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity. [ABSTRACT FROM AUTHOR]

Bladder cancer is the fifth most commonly diagnosed non-cutaneous solid malignancy, and the second most commonly diagnosed genitourinary malignancy amongst people living in the United States, where it is estimated that more than 61,000 new cases of bladder cancer will be diagnosed in the year 2008. Approximately 90% of malignant tumors arising in the urinary bladder are of epithelial origin, the majority being transitional cell carcinomas. Early stage bladder tumors have been classified into two groups with distinct behavior and unique molecular profiles: low grade tumors (always papillary and usually superficial), and high-grade tumors (either papillary or non-papillary, and often invasive). Clinically, superficial bladder tumors (stages Ta and Tis) account for 75% to 85% of neoplasms, while the remaining 15% to 25% are invasive (T1, T2-T4) or metastatic lesions at the time of initial presentation. Studies from the author's group and others have revealed that distinct genotypic and phenotypic patterns are associated with early versus late stages of bladder cancer. Most importantly, early superficial diseases appear to segregate into two main pathways. Superficial papillary bladder tumors are characterized by gain-of-function mutations, mainly affecting classical oncogenes such as RAS and FGFR3. Deletions of chromosome 9, mainly allelic losses on the long arm (9q) are also frequent events in these tumors. Such genetic alterations are observed in most if not all superficial papillary non-invasive tumors (Ta), but only in a small subset of invasive bladder neoplasms. Flat carcinoma in situ (Tis) and invasive tumors are characterized by loss-of-function mutations, affecting the prototype tumor suppressor genes, including p53, RB and PTEN. These alterations are absent or very rare in the Ta tumors analyzed, but have been frequently identified in invasive bladder carcinomas. Based on these data, a novel model for bladder tumor progression has been proposed in which two separate genetic pathways characterize the evolution of superficial bladder neoplasms. Numerous individual molecular markers have been identified in the tissue specimens that correlate to some extent with tumor stage, and possibly with prognosis in bladder cancer. However, these molecular prognosticators do not play a role in the clinical routine management of patients with bladder tumors, mainly due to lack of large prospective validation studies. Thus, the need for development of specific tissue and serum tumor markers for prognostic stratification remains. The advent of high-throughput microarrays technologies allows comprehensive discovery of targets relevant in bladder cancer progression, which could be translated into new approaches for drug and biomarker development. Further investigation is warranted to define novel biomarkers specific for bladder cancer patients based on the molecular alterations of tumor progression, and multiplexed strategies for clinical management. [ABSTRACT FROM AUTHOR]

Cadmium is a known carcinogen that has been implicated in prostate cancer, but how it affects prostate carcinogenesis in humans remains unclear. Evidence from basic science suggests that cadmium can bind to the androgen receptor causing endocrine disruption. The androgen receptor is required for normal prostate development and is the key driver of prostate cancer progression. In this study, we examined the association between cadmium content and androgen receptor protein expression in prostate cancer tissue of African American (N = 22) and European American (N = 30) men. Although neither overall tumor cadmium content (log transformed) nor androgen receptor protein expression level differed by race, we observed a race-cadmium interaction with regard to androgen receptor expression (P = 0.003) even after accounting for age at prostatectomy, smoking history, and Gleason score. African American men had a significant positive correlation between tumor tissue cadmium content and androgen receptor expression (Pearson correlation = 0.52, P = 0.013), while European Americans showed a non-significant negative correlation between the two (Pearson correlation = -0.19, P = 0.31). These results were unchanged after further accounting for tissue zinc content or dietary zinc or selenium intake. African American cases with high-cadmium content (>median) in tumor tissue had more than double the androgen receptor expression (0.021 vs. 0.008, P = 0.014) of African American men with low-cadmium level. No difference in androgen receptor expression was observed in European Americans by cadmium level (high 0.015 vs. low 0.011, P = 0.30). Larger studies are needed to confirm these results and if upheld, determine the biologic mechanism by which cadmium increases androgen receptor protein expression in a race-dependent manner. Our results suggest that cadmium may play a role in race disparities observed in prostate cancer., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Objective: To compare the performance of a systems-based risk assessment tool with standard defined risk groups and the 10-year postoperative nomogram for predicting disease progression, including biochemical relapse and clinical (systemic) failure., Patients and Methods: Clinical variables, biometric profiles and outcome results from a training cohort comprising 373 patients in a published postoperative systems-based prognostic model were obtained. Patients were stratified according to D'Amico standard risk groups, Kattan 10-year postoperative nomogram and prognostic scores from the postoperative tissue model. The association of pathological variables and calculated risk groups with biochemical recurrence and clinical (systemic) failure was assessed using the concordance index (C-index) and hazard ratio (HR)., Results: Systems-based post-prostatectomy models to predict significant disease progression (post-treatment clinical failure) were more accurate than the D'Amico defined risk groups and the Kattan 10-year postoperative nomogram (systems model: C-index, 0.84; HR, 17.46; P < 0.001 vs D'Amico: C-index, 0.73; HR, 11; P = 0.001; 10-year nomogram: C-index, 0.79; HR, 5.06; P < 0.001). The systems models were also more accurate than standard risk groups for predicting prostate-specific antigen recurrence (systems model: C-index, 0.76; HR, 8.94; P < 0.001 vs D'Amico C- index, 0.70; HR, 4.67; P < 0.001) and showed incremental improvement over the 10-year postoperative nomogram (C-index, 0.75; HR, 5.83; P < 0.001). The postoperative tissue model provided additional risk discrimination over surgical margin status and extracapsular extension for predicting disease outcome, and was most significant for the clinical (systemic) failure endpoint (surgical margin: C-index, 0.58; HR, 1.57; P= 0.2; extracapsular extension: C-index, 0.62; HR, 2.06; P = 0.04)., Conclusions: Risk assessment models that incorporate characteristics from the patient's own tumour specimen are more accurate than clinical-only nomograms for predicting significant disease outcome. Systems-based tools should provide useful information concerning the appropriate receipt of adjuvant therapy in the post-surgical setting., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)