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1.
Int J Mol Sci ; 23(2)2022 Jan 13.
Article in English | MEDLINE | ID: covidwho-1884201

ABSTRACT

Colorectal cancer (CRC) is still a leading cause of cancer death worldwide. Less than half of cases are diagnosed when the cancer is locally advanced. CRC is a heterogenous disease associated with a number of genetic or somatic mutations. Diagnostic markers are used for risk stratification and early detection, which might prolong overall survival. Nowadays, the widespread use of semi-invasive endoscopic methods and feacal blood tests characterised by suboptimal accuracy of diagnostic results has led to the detection of cases at later stages. New molecular noninvasive tests based on the detection of CRC alterations seem to be more sensitive and specific then the current methods. Therefore, research aiming at identifying molecular markers, such as DNA, RNA and proteins, would improve survival rates and contribute to the development of personalized medicine. The identification of "ideal" diagnostic biomarkers, having high sensitivity and specificity, being safe, cheap and easy to measure, remains a challenge. The purpose of this review is to discuss recent advances in novel diagnostic biomarkers for tumor tissue, blood and stool samples in CRC patients.


Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/etiology , Early Detection of Cancer/methods , Clinical Decision-Making , Colorectal Neoplasms/metabolism , Disease Management , Disease Susceptibility , Feces/chemistry , Humans , Liquid Biopsy/methods , Precision Medicine/methods , Volatile Organic Compounds
2.
Cancer Sci ; 113(4): 1531-1534, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1779205

ABSTRACT

According to the current international guidelines, high-risk patients diagnosed with pathological T1 (pT1) colorectal cancer (CRC) who underwent complete local resection but may have risk of developing lymph node metastasis (LNM) are recommended additional intestinal resection with lymph node dissection. However, around 90% of the patients without LNM are exposed to the risk of being overtreated due to the insufficient pathological criteria for risk stratification of LNM. Circulating tumor DNA (ctDNA) is a noninvasive biomarker for molecular residual disease and relapse detection after treatments including surgical and endoscopic resection of solid tumors. The CIRCULATE-Japan project includes a large-scale patient-screening registry of the GALAXY study to track ctDNA status of patients with stage II to IV or recurrent CRC that can be completely resected. Based on the CIRCULATE-Japan platform, we launched DENEB, a new prospective study, within the GALAXY study for patients with pT1 CRC who underwent complete local resection and were scheduled for additional intestinal resection with lymph node dissection based on the standard pathologic risk stratification criteria for LNM. The aim of this study is to explore the ability of predicting LNM using ctDNA analysis compared with the standard pathological criteria. The ctDNA assay will build new evidence to establish a noninvasive personalized diagnosis in patients, which will facilitate tailored/optimal treatment strategies for CRC patients.


Subject(s)
Circulating Tumor DNA , Colorectal Neoplasms , Circulating Tumor DNA/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Humans , Liquid Biopsy , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prospective Studies , Retrospective Studies , Risk Factors
3.
Biosens Bioelectron ; 196: 113698, 2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1466073

ABSTRACT

Liquid biopsy technologies have seen a significant improvement in the last decade, offering the possibility of reliable analysis and diagnosis from several biological fluids. The use of these technologies can overcome the limits of standard clinical methods, related to invasiveness and poor patient compliance. Along with this there are now mature examples of lab-on-chips (LOC) which are available and could be an emerging and breakthrough technology for the present and near-future clinical demands that provide sample treatment, reagent addition and analysis in a sample-in/answer-out approach. The possibility of combining non-invasive liquid biopsy and LOC technologies could greatly assist in the current need for minimizing exposure and transmission risks. The recent and ongoing pandemic outbreak of SARS-CoV-2, indeed, has heavily influenced all aspects of life worldwide. Ordinary tasks have been forced to switch from "in presence" to "distanced", limiting the possibilities for a large number of activities in all fields of life outside of the home. Unfortunately, one of the settings in which physical distancing has assumed noteworthy consequences is the screening, diagnosis and follow-up of diseases. In this review, we analyse biological fluids that are easily collected without the intervention of specialized personnel and the possibility that they may be used -or not-for innovative diagnostic assays. We consider their advantages and limitations, mainly due to stability and storage and their integration into Point-of-Care diagnostics, demonstrating that technologies in some cases are mature enough to meet current clinical needs.


Subject(s)
Biosensing Techniques , COVID-19 , Neoplasms , Humans , Liquid Biopsy , Neoplasms/diagnosis , Neoplasms/epidemiology , Pandemics , SARS-CoV-2
4.
Immunology ; 164(1): 1-2, 2021 09.
Article in English | MEDLINE | ID: covidwho-1354493

ABSTRACT

Mass vaccination of the global population against SARS-CoV-2 will, we hope, turn the tide against this devastating pandemic. To complement vaccinations, better tools are needed to enable viral infections and immunological protection to be monitored. Accurate tools provide sound data for informed decision-making at many levels, from personal to governmental. The measurement of viral RNA is currently routinely used to detect active infections, but only gives a positive result during infection and is unable to reveal historic infections. Tests involving a detection of SARS-CoV-2-specific antibodies can reveal prior exposures to virus and can measure anti-viral immune responses induced after natural infection or after vaccination. They may eventually also be used to predict an individual's likelihood of becoming re-infected. Here, we report on the development of a sensitive ELISA technique to detect multiple isotypes of antibodies against the spike glycoprotein, in samples of both serum and saliva. This paper provides an important step towards understanding the immune response to SARS-CoV-2 and may therefore eventually help us to effectively control it.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Viral/blood , Antibody Specificity , COVID-19/blood , COVID-19/diagnosis , Disease Susceptibility , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/standards , Host-Pathogen Interactions/immunology , Humans , Liquid Biopsy , Sensitivity and Specificity , Viral Load
5.
Cells ; 10(6)2021 06 10.
Article in English | MEDLINE | ID: covidwho-1264420

ABSTRACT

The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients.


Subject(s)
COVID-19/diagnosis , Leukocytes, Mononuclear/microbiology , Lung/microbiology , Microbiota/physiology , Bronchoalveolar Lavage Fluid/microbiology , Bronchoalveolar Lavage Fluid/virology , COVID-19/immunology , COVID-19/microbiology , COVID-19/virology , Case-Control Studies , Humans , Leukocytes, Mononuclear/virology , Liquid Biopsy , Lung/pathology , Lung/virology , Microbiota/genetics , Microbiota/immunology , Prognosis , RNA, Bacterial/analysis , RNA, Fungal/analysis , RNA-Seq , SARS-CoV-2/physiology
7.
RNA Biol ; 18(5): 688-695, 2021 05.
Article in English | MEDLINE | ID: covidwho-1061120

ABSTRACT

The COVID-19 emergency pandemic resulting from infection with SARS-CoV-2 represents a major threat to public health worldwide. There is an urgent clinical demand for easily accessible tools to address weaknesses and gaps in the management of COVID-19 patients. In this context, transcriptomic profiling of liquid biopsies, especially microRNAs (miRNAs), has recently emerged as a robust source of potential clinical indicators for medical decision-making. Nevertheless, the analysis of the circulating miRNA signature and its translation to clinical practice requires strict control of a wide array of methodological details. In this review, we indicate the main methodological aspects that should be addressed when evaluating the circulating miRNA profiles in COVID-19 patients, from preanalytical and analytical variables to the experimental design, impact of confounding, analysis of the data and interpretation of the findings, among others. Additionally, we provide practice points to ensure the rigour and reproducibility of miRNA-based biomarker investigations of this condition.Abbreviations: ACE: angiotensin-converting enzyme; ARDS: acute respiratory distress syndrome; COVID-19: coronavirus disease 2019; ERDN: early Detection Research Network; LMWH: low molecular weight heparin; miRNA: microRNA; ncRNA: noncoding RNA; SARS-CoV-2: severe acute respiratory syndrome coronavirus-2; SOP: standard operating procedure.


Subject(s)
COVID-19/blood , COVID-19/genetics , Gene Expression Profiling/methods , MicroRNAs/blood , MicroRNAs/genetics , SARS-CoV-2 , COVID-19/virology , Gene Expression Profiling/standards , Genetic Markers , Humans , Liquid Biopsy/methods , Liquid Biopsy/standards , MicroRNAs/isolation & purification , Pandemics , Virus Inactivation
8.
J Biomech ; 117: 110235, 2021 03 05.
Article in English | MEDLINE | ID: covidwho-1042535

ABSTRACT

Microfluidic devices can be thought of as comprising interconnected miniaturized compartments performing multiple experimental tasks individually or in parallel in an integrated fashion. Due to its small size, portability, and low cost, attempts have been made to incorporate detection assays into microfluidic platforms for diseases such as cancer and infection. Some of these technologies have served as point-of-care and sample-to-answer devices. The methods for detecting biomarkers in different diseases usually share similar principles and can conveniently be adapted to cope with arising health challenges. The COVID-19 pandemic is one such challenge that is testing the performance of both our conventional and newly-developed disease diagnostic technologies. In this mini-review, we will first look at the progress made in the past few years in applying microfluidics for liquid biopsy and infectious disease detection. Following that, we will use the current pandemic as an example to discuss how such technological advancements can help in the current health challenge and better prepare us for future ones.


Subject(s)
COVID-19 Testing , COVID-19/diagnosis , Liquid Biopsy/methods , Microfluidics/methods , Point-of-Care Testing , Biomarkers , Circulating Tumor DNA , Exosomes , Humans , Lab-On-A-Chip Devices , Machine Learning , Neoplasms/diagnosis , Neoplastic Cells, Circulating
9.
BMJ ; 372: m4933, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1007304
10.
Expert Rev Mol Diagn ; 21(1): 101-107, 2021 01.
Article in English | MEDLINE | ID: covidwho-962282

ABSTRACT

Background: The SARS-CoV-2 pandemic introduced a global distraction effect in cancer patients' care. The aim of this study was to explore the effect of the pandemic on the largest molecular diagnostics center for cancer patients and high-risk individuals in Serbia.Research design and methods: EGFR, KRAS/NRAS, BRAF, and BRCA1/2 mutation testing were performed by qPCR and NGS. NGS was used for panel testing of hereditary breast/ovarian cancer and cancers associated with Lynch syndrome. The analytical output during the state of emergency (SoE) was compared to the period before and after the outbreak using one-way ANOVA. Statistical significance was set at p < 0.05.Results: A 38% reduction in the number of analysis was detected during the SoE. After the SoE, a 19% reduction was noted compared to SoE and 50% compared to the period before the SoE (p = 0.038). Three of the 48 scheduled appointments for pretest genetic counseling were carried out during the SoE, but the number of NGS tests increased by 50%.Conclusions: The SARS-CoV-2 pandemic had a profound negative effect on the diagnostic output of our centralized molecular diagnostics center. The only positive effect was shortening of waiting lists for hereditary cancer patients and high-risk individuals.


Subject(s)
Breast Neoplasms/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Mutation , Ovarian Neoplasms/diagnosis , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/genetics , COVID-19 , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Mutational Analysis , ErbB Receptors/genetics , Female , GTP Phosphohydrolases/genetics , Genetic Counseling , Genetic Predisposition to Disease , Humans , Liquid Biopsy , Membrane Proteins/genetics , Ovarian Neoplasms/genetics , Pandemics , Pathology, Molecular , Pharmacogenetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Serbia/epidemiology
12.
Transplant Proc ; 52(9): 2592-2595, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-720725

ABSTRACT

BACKGROUND: Kidney allograft biopsy is the gold standard for diagnosis of rejection. Under the current extraordinary circumstances of the coronavirus disease 2019 (COVID-19), in which social distancing is key to limiting the spread of the virus, the model used to provide care to transplant recipients has undergone a very rapid transformation. In the spirit of medical distancing, we have been using the donor-derived cell-free DNA (dd-cfDNA) test for screening for rejection. METHODS: This article describes our experience with this approach between March 15th and May 20th, 2020. RESULTS: This test was obtained for-cause in 23 patients and for monitoring in 9 patients. Normal results aided in forgoing biopsy in 63% of the patients for whom the test was obtained in the outpatient setting. The test is neither 100% sensitive nor specific for rejection; however, when used in combination with the available clinical information, it can be used for determining whether bringing in a transplant recipient into a medical facility is necessary. CONCLUSIONS: In the event COVID-19 becomes a long-term challenge for our community, noninvasive biomarkers such as the dd-cfDNA may become more relevant than ever in enhancing our ability to care for our transplant patients while maximizing the distancing measures.


Subject(s)
Cell-Free Nucleic Acids/analysis , Coronavirus Infections/prevention & control , Disease Transmission, Infectious/prevention & control , Graft Rejection/diagnosis , Kidney Transplantation/adverse effects , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Adult , Allografts/chemistry , Betacoronavirus , Biomarkers/analysis , COVID-19 , Coronavirus Infections/transmission , Female , Humans , Kidney/chemistry , Liquid Biopsy , Male , Middle Aged , Pneumonia, Viral/transmission , SARS-CoV-2 , Transplantation, Homologous
13.
J Immunother Cancer ; 8(2)2020 08.
Article in English | MEDLINE | ID: covidwho-712954

ABSTRACT

To report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified with clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated with immune checkpoint inhibitors. Retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) and MSI-H tumor detected by a commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September 2018 to April 2020. From a total of 14 MSI-H metastatic prostate cancer patients at participating centers, nine patients with mCRPC with 56% bone, 33% nodal, 11% liver and 11% soft-tissue metastases and a median PSA of 29.3 ng/dL, were treated with pembrolizumab after 2 lines of therapy for CRPC. The estimated median time on pembrolizumab was 9.9 (95% CI 1.0 to 18.8) months. Four patients (44%) achieved PSA50 after a median of 4 (3-12) weeks after treatment initiation including three patients with >99% PSA decline. Among the patients evaluable for radiographic response (n=5), the response rate was 60% with one complete response and two partial responses. Best response was observed after a median of 3.3 (1.4-7.6) months. At time of cut-off, four patients were still on pembrolizumab while four patients discontinued therapy due to progressive disease and one due to COVID-19 infection. Half of the patients with PSA50 had both MSI-H and pathogenic alterations in BRCA1 and BRCA2 in their G360 assays. The use of liquid biopsy to identify metastatic prostate cancer patients with MSI-H is feasible in clinical practice and may overcome some of the obstacles associated with prostate cancer tumor tissue testing. The robust activity of pembrolizumab in selected patients supports the generalized testing for MSI-H.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Microsatellite Instability , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Biomarkers, Tumor/genetics , COVID-19 , Circulating Tumor DNA/blood , Coronavirus Infections , Humans , Liquid Biopsy , Male , Middle Aged , Mutation , Pandemics , Pneumonia, Viral , Prostatic Neoplasms/pathology
14.
Cancer Cytopathol ; 128(12): 905-909, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-696749

ABSTRACT

BACKGROUND: Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents the causative agent of a potentially fatal disease. The spread of the infection and the severe clinical disease have led to the widespread adoption of social distancing measures. Special attention and efforts to protect or reduce transmission have been applied at all social levels, including health care operators. Hence, this reports focuses on the description of a new protocol for the safe management of cytological samples processed by liquid-based cytology (LBC) with an evaluation of the changes in terms of morphology and immunoreactivity. METHODS: From March 11 to April 25, 2020, 414 cytological cases suspicious for SARS-CoV-2 were processed with a new virus-inactivating method suggested by Hologic, Inc, for all LBC specimens. RESULTS: The samples showed an increased amount of fibrin in the background. A slight decrease in cellular size was also observed in comparison with the standard method of preparation. Nonetheless, the nuclear details of the neoplastic cells were well identified, and the immunoreactivity of the majority of those cells was maintained. The cell blocks did not show significant differences in morphology, immunoreactivity, or nucleic acid stability. CONCLUSIONS: Despite some minor changes in the morphology of the cells, the results of this study highlight that the adoption of the new protocol for the biosafety of LBC-processed samples in pathology laboratories is important for minimizing the risk for personnel, trainees, and cytopathologists without impairing the diagnostic efficacy of the technique.


Subject(s)
COVID-19/diagnosis , Containment of Biohazards/standards , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Laboratories, Hospital/standards , Specimen Handling/standards , COVID-19/pathology , COVID-19/prevention & control , COVID-19/transmission , Clinical Protocols/standards , Containment of Biohazards/trends , Histocytological Preparation Techniques/methods , Histocytological Preparation Techniques/standards , Humans , Laboratories, Hospital/trends , Liquid Biopsy , Pandemics/prevention & control , Pathologists/standards , Pathology, Clinical/standards , Personal Protective Equipment/standards , Risk Factors , SARS-CoV-2/isolation & purification , Specimen Handling/methods
15.
Eur Urol Focus ; 6(5): 1086-1096, 2020 Sep 15.
Article in English | MEDLINE | ID: covidwho-591878

ABSTRACT

CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that erupted in December 2019 has affected more than a million people from over 200 countries, claiming over 70 000 lives (by April 7, 2020). As the viral infection is driven by increased angiotensin-converting enzyme-2 (ACE2) expression, with the kidney exhibiting the highest expression, it is crucial to gain insights into the mechanisms underlying renal cell carcinoma (RCC) and coronavirus disease 2019 (COVID-19). OBJECTIVE: This study considers up-to-date information on the biological determinants shared by COVID-19 and renal disease, and aims to provide evidence-based recommendations for the clinical management of RCC patients with COVID-19. EVIDENCE ACQUISITION: A literature search was performed using all sources (MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science). As of March 31, 2020, the Center for Disease Control reported that of the adults hospitalized for COVID-19 with underlying conditions in the USA, 74.8% had chronic renal disease. EVIDENCE SYNTHESIS: Evidence is discussed from epidemiological studies on SARS-CoV-2 pandemic and molecular studies on the role of kidney in facilitating routes for SARS-CoV-2 entry, leading to increased virulence of SARS-CoV-2 and clinical manifestation of symptoms in RCC. CONCLUSIONS: This analysis will advance our understanding of (1) the molecular signatures shared by RCC and COVID-19 and (2) the clinical implications of overlapping signaling pathways in the therapeutic management of RCC and COVID-19 patients. PATIENT SUMMARY: Amid the coronavirus disease 2019 (COVID-19) pandemic, patients diagnosed with renal cell carcinoma and infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may receive complimentary treatment modalities to enhance therapeutic response.


Subject(s)
Betacoronavirus/metabolism , Carcinoma, Renal Cell/metabolism , Coronavirus Infections/metabolism , Kidney Neoplasms/metabolism , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Renal Insufficiency, Chronic/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Acute Kidney Injury/epidemiology , Acute Kidney Injury/metabolism , Acute Kidney Injury/therapy , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Carcinoma, Renal Cell/epidemiology , Comorbidity , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Endothelin Receptor Antagonists/therapeutic use , Hospitalization , Humans , Ipilimumab/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/epidemiology , Liquid Biopsy , Nivolumab/therapeutic use , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Protein Kinase Inhibitors/therapeutic use , Renal Dialysis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , SARS-CoV-2 , Serine Endopeptidases/metabolism , Severity of Illness Index , Sunitinib/therapeutic use
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