COVID-19 SCREENING AND MONITORING OF ASYMPTOMATIC HEALTH WORKERS WITH A RAPID SEROLOGICAL TEST

BackgroundHealth workers are at high risk for SARS-CoV-2 infection and, if asymptomatic, for transmitting the virus on to fragile cancer patients. Materials and methodWe monitored health care workers (HCW) of our Cancer Institute with the rapid serological test Viva-DiagTM analyzing COVID-19 associated-IgG/IgM. Test were performed at time 0 and after 14 days; Rt-PCR and CLIA assays were also perfoRmed in positive Viva-DiagTM cases. 606 and 393 HCW had blood sample taken at time 0 and 14, respectively. ResultsOverall, 9 HCW (1.5%) resulted not-negative at Viva-DiagTM and one of them was confirmed positive for SARS-COV2 infection at RT-PCR oropharingeal swab. At time 0, all 9 cases showed some IgM expression and only one IgG; after 14 days IgM persisted in all cases while IgG became evident in 4 ones. A parallel CLIA test was performed in 23 quaratined subjetcs and in all Viva-Diag not negative cases. CLIA confirmed a positive level of IgM in 5/13 positive Viva-Diag cases; conversely, IgG was confirmed positive at CLIA in 4/5 cases positive at Viva-Diag. These results pose the question of different performances of the two tests. ConclusionsOur study suggest that Viva-Diag assay can be of help in individualizing SARS_COV2 infected people fisrt of all in cohorts of subjetcs with high prevalence. Different performances of serological colorimetric and CLIA tools remain to be ascertained.

RAPID SEROLOGICAL TESTS HAVE A ROLE IN ASYMPTOMATIC HEALTH WORKERS COVID-19 SCREENING

Health workers are at high risk for SARS-CoV-2 infection and, if asymptomatic, for transmitting the virus on to fragile cancer patients. We screened 525 health workers of our Cancer Institute with rapid serological test Viva-Diag analyzingCOVID-19 associated-IgG/IgM. Six subjects (1,1%) resulted with Viva-Diag test not-negative for IgM. All 6 cases had RT-PCR SARS-CoV-2 test negative; repeating analysis ofIgG/IgM expression by CLIA assay also, 2 cases resulted IgM positive and 1 case IgG/IgM positive. This latter subject reported a contact with an infected SARS-CoV-2 person, a month earlier.In conclusion our study seems to suggest: a) a different analytical sensitivity inIgG/IgM evaluation for Viva-Diag and CLIA assays needing to be further determined; b) the ability of Viva-Diagrapid COVID-19 test to evidence health workers positive for Immunoglobulins expression. Discordant results of rapid serological tests with respect to RT-PCR stress the different clinical meaning the two assays can have, question clearly referring to further studies to optimize the utilization of rapid serological test in asymptomatic subjects at high risk for infection.

Proteomic profile and in silico analysis in metastatic melanoma with and without BRAF mutation.

INTRODUCTION: Selective inhibitors of BRAF, vemurafenib and dabrafenib are the standard of care for metastatic melanoma patients with BRAF V600, while chemotherapy continued to be widely used in BRAF wild type patients. MATERIALS AND METHODS: In order to discover novel candidate biomarkers predictive to treatment, serum of 39 metastatic melanoma vemurafenib (n = 19) or chemotherapy (n = 20) treated patients at baseline, at disease control and at progression, were analyzed using SELDI-TOF technology. In silico analysis was used to identify more significant peaks. RESULTS: In patients with different BRAF status, we found 5 peptides significantly deregulated, with the down-regulation of the m/z 9176 peak strongly associated with BRAF mutation. At baseline as predictive biomarkers we identified 2 peptides - m/z 6411, 4075 - as significantly up-regulated in responders to chemotherapy and 4 peaks - m/z 5900, 12544, 49124 and 11724 - significantly up-regulated in longer vs shorter responders to vemurafenib. After response, 3 peptides (m/z 4658, 18639, and 9307) resulted significantly down regulated while 3 peptides m/z 9292, 7765 and 9176 appeared up-regulated respectively in chemotherapy and vemurafenib responder patients. In vemurafenib treated patients, 16 peaks appeared deregulated at progression compared to baseline time. In silico analysis identified proteins involved in invasiveness (SLAIN1) and resistance (ABCC12) as well as in the pathway of detoxification (NQO1) and apoptosis (RBM10, TOX3, MTEFD1, TSPO2). Proteins associated with the modulation of neuronal plasticity (RIN1) and regulatory activity factors of gene transcription (KLF17, ZBTB44) were also highlighted. CONCLUSION: Our exploratory study highlighted some factors that deserve to be further investigated in order to provide a framework for improving melanoma treatment management through the development of biomarkers which could act as the strongest surrogates of the key biological events in stage IV melanoma.

Changes in CpG islands promoter methylation patterns during ductal breast carcinoma progression.

Aberrant promoter methylation of several known or putative tumor suppressor genes occurs frequently during carcinogenesis, and this epigenetic change has been considered as a potential molecular marker for cancer. We examined the methylation status of nine genes (APC, CDH1, CTNNB1, TIMP3, ESR1, GSTP1, MGMT, THBS1, and TMS1), by quantitative methylation specific PCR. Synchronous preinvasive lesions (atypical ductal hyperplasia and/or ductal carcinoma in situ) and invasive ductal breast carcinoma from 52 patients, together with pure lesions from 24 patients and 12 normal tissues paired to tumor and 20 normal breast distant from tumor were analyzed. Aberrant promoter methylation was detected in both preinvasive and invasive lesions for genes APC, CDH1, CTNNB1, TIMP3, ESR1, and GSTP1. However, hierarchical mixed model and Generalized Estimating Equations model analyses showed that only APC, CDH1, and CTNNB1 promoter regions showed a higher frequency and methylation levels in pathologic samples when compared with normal breast. Whereas APC and CTNNB1 did not show differences in methylation levels or frequencies, CDH1 showed higher methylation levels in invasive tumors as compared with preinvasive lesions (P < 0.04, Mann-Whitney test with permutation correction). The analysis of APC, CDH1, and CTNNB1 methylation status was able to distinguish between normal and pathologic samples with a sensitivity of 67% (95% confidence interval, 60-71%) and a specificity of 75% (95% confidence interval, 69-81%). Our data point to the direct involvement of APC, CDH1, and CTNNB1 promoter methylation in the early stages of breast cancer progression and suggest that they may represent a useful tool for the detection of tumor cells in clinical specimens.

Identification of tumor evolution patterns by means of inductive logic programming / 基因组蛋白质组与生物信息学报·英文版

In considering key events of genomic disorders in the development and progression of cancer, the correlation between genomic instability and carcinogenesis is currently under investigation. In this work, we propose an inductive logic programming approach to the problem of modeling evolution patterns for breast cancer. Using this approach, it is possible to extract fingerprints of stages of the disease that can be used in order to develop and deliver the most adequate therapies to patients. Furthermore, such a model can help physicians and biologists in the elucidation of molecular dynamics underlying the aberrations-waterfall model behind carcinogenesis. By showing results obtained on a real-world dataset, we try to give some hints about further approach to the knowledge-driven validations of such hypotheses.