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1.
Cytopathology ; 33(1): 23-38, 2022 01.
Article in English | MEDLINE | ID: covidwho-1799272

ABSTRACT

Lung cancer is a leading cause of cancer mortality worldwide but recent years have seen a rapidly rising proportion of cases of advanced non-small cell carcinoma amenable to increasingly targeted therapy, initially based on the differential response to systemic treatment of tumours of squamous or glandular differentiation. In two-thirds of the cases, where patients present with advanced disease, both primary pathological diagnosis and biomarker testing is based on small biopsies and cytopathological specimens. The framework of this article is an overview of the technical aspect of each stage of the specimen pathway with emphasis on maximising potential for success when using small cytology samples. It brings together the current literature addressing pre-analytical and analytical aspects of specimen acquisition, performing rapid onsite evaluation, and undertaking diagnostic and predictive testing using immunocytochemistry and molecular platforms. The advantages and drawbacks of performing analysis on cell block and non-cell block specimen preparations is discussed.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma , Lung Neoplasms , Biomarkers, Tumor/metabolism , Carcinoma/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung/pathology , Lung Neoplasms/pathology
2.
Int J Mol Sci ; 22(16)2021 Aug 05.
Article in English | MEDLINE | ID: covidwho-1674661

ABSTRACT

Breast cancers and cancers of the genitourinary tract are the most common malignancies among men and women and are still characterized by high mortality rates. In order to improve the outcomes, early diagnosis is crucial, ideally by applying non-invasive and specific biomarkers. A key role in this field is played by extracellular vesicles (EVs), lipid bilayer-delimited structures shed from the surface of almost all cell types, including cancer cells. Subcellular structures contained in EVs such as nucleic acids, proteins, and lipids can be isolated and exploited as biomarkers, since they directly stem from parental cells. Furthermore, it is becoming even more evident that different body fluids can also serve as sources of EVs for diagnostic purposes. In this review, EV isolation and characterization methods are described. Moreover, the potential contribution of EV cargo for diagnostic discovery purposes is described for each tumor.


Subject(s)
Breast Neoplasms/diagnosis , Extracellular Vesicles/metabolism , Urogenital Neoplasms/diagnosis , Animals , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Early Detection of Cancer/methods , Female , Humans , Neoplasms/diagnosis , Neoplasms/metabolism , Nucleic Acids/metabolism , Urogenital Neoplasms/metabolism
3.
J Cancer Res Clin Oncol ; 148(3): 599-608, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1527467

ABSTRACT

INTRODUCTION: Cathepsin L (CTSL) is a kind of the SARS-entry-associated CoV-2's proteases, which plays a key role in the virus's entry into the cell and subsequent infection. We investigated the association between the expression level of CTSL and overall survival in Glioblastoma multiforme (GBM) patients, to better understand the possible route and risks of new coronavirus infection for patients with GBM. METHODS: The expression level of CTSL in GBM was analyzed using TCGA and CGGA databases. The relationship between CTSL and immune infiltration levels was analyzed by means of the TIMER database. The impact of CTSL inhibitors on GBM biological activity was tested. RESULTS: The findings revealed that GBM tissues had higher CTSL expression levels than that of normal brain tissues, which was associated with a significantly lower survival rate in GBM patients. Meanwhile, the expression level of CTSL negatively correlated with purity, B cell and CD8+ T cell in GBM. CTSL inhibitor significantly reduced growth and induced mitochondrial apoptosis. CONCLUSION: According to the findings, CTSL acts as an independent prognostic factor and can be considered as promising therapeutic target for GBM.


Subject(s)
Biomarkers, Tumor/metabolism , COVID-19/pathology , Cathepsin L/metabolism , Dipeptides/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Glioblastoma/pathology , Apoptosis , COVID-19/drug therapy , COVID-19/enzymology , COVID-19/virology , Case-Control Studies , Cell Proliferation , Female , Glioblastoma/drug therapy , Glioblastoma/enzymology , Humans , Male , Middle Aged , Prognosis , SARS-CoV-2/physiology , Survival Rate , Tumor Cells, Cultured
4.
Int J Biol Sci ; 17(1): 20-31, 2021.
Article in English | MEDLINE | ID: covidwho-1526974

ABSTRACT

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global infection, and is seriously threatening human life, especially cancer patients. Thus, we sought to determine the clinical roles of ACE2 (the cell entry receptor of SARS-CoV-2) in ccRCC (clear cell renal cell carcinoma). TCGA, GEO and TIP datasets, and immunohistochemistry and western blot results were used to determine the prognostic and clinicopathological characteristics of ACE2. ACE2 expression was down-regulated in ccRCC tissues and cell lines. The multivariate Cox regression analysis results indicated that increased ACE2 expression was independent predictor of longer OS (HR: 0.8259, 95%CI: 0.7734-0.8819, P<0.0001) and RFS (HR: 0.8023, 95%CI: 0.7375-0.8729, P<0.0001) in ccRCC patients. Lower ACE2 expression was also associated with advanced tumor stage, higher histological grade and pathological stage, and metastasis. Besides, ACE2 expression was significantly positively and negatively correlated with CD4 Naïve infiltration and CD4 Memory infiltration, respectively. Moreover, higher CD4 Naïve and lower CD4 Memory infiltration levels were associated with better pathological features and longer OS and RFS. Furthermore, high ACE2 expression group in decreased CD4 Naïve, enriched CD4 Naïve and enriched CD4 memory cohort had favorable prognosis. These findings identified that AEC2 was significantly reduced in ccRCC, and decreased ACE2 was related to worse pathological features and poor prognosis. Low ACE2 expression in ccRCC may partially affect the prognosis due to altered immune cells infiltration levels.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/metabolism , CD4-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19/metabolism , COVID-19/virology , Carcinoma, Renal Cell/immunology , Humans , Kidney Neoplasms/immunology , Prognosis , SARS-CoV-2/isolation & purification
5.
Environ Sci Pollut Res Int ; 29(15): 22012-22030, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1514070

ABSTRACT

Coronavirus disease 2019 (COVID-19) continues as a global pandemic. Patients with lung cancer infected with COVID-19 may develop severe disease or die. Treating such patients severely burdens overwhelmed healthcare systems. Here, we identified potential pathological mechanisms shared between patients with COVID-19 and lung adenocarcinoma (LUAD). Co-expressed, differentially expressed genes (DEGs) in patients with COVID-19 and LUAD were identified and used to construct a protein-protein interaction (PPI) network and to perform enrichment analysis. We used the NetworkAnalyst platform to establish a co-regulatory of the co-expressed DEGs, and we used Spearman's correlation to evaluate the significance of associations of hub genes with immune infiltration and immune checkpoints. Analysis of three datasets identified 112 shared DEGs, which were used to construct a protein-PPI network. Subsequent enrichment analysis revealed co-expressed genes related to biological process (BP), molecular function (MF), and cellular component (CC) as well as to pathways, specific organs, cells, and diseases. Ten co-expressed hub genes were employed to construct a gene-miRNA, transcription factor (TF)-gene, and TF-miRNA network. Hub genes were significantly associated with immune infiltration and immune checkpoints. Finally, methylation level of hub genes in LUAD was obtained via UALCAN database. The present multi-dimensional study reveals commonality in specific gene expression by patients with COVID-19 and LUAD. These findings provide insights into developing strategies for optimising the management and treatment of patients with LUAD with COVID-19.


Subject(s)
Adenocarcinoma of Lung , COVID-19 , Lung Neoplasms , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , COVID-19/genetics , Computational Biology/methods , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology
6.
Int J Biol Macromol ; 193(Pt A): 838-846, 2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1487745

ABSTRACT

Discovery of robust, selective and specific biomarkers are important for early diagnosis and monitor progression of human diseases. Eye being a common target for several human diseases, vision impediment and complications are often associated with systemic and ocular diseases. Tears are bodily fluids that are closest to eye and are rich in protein content and other metabolites. As a biomarker repository, it advantages over other bodily fluids due to the ability to collect it non-invasively. In this review, we highlight some recent advancements in identification of tear-based protein biomarkers like lacryglobin and cystatin SA for cancer; interleukin-6 and immunoglobulin-A antibody for COVID-19; tau, amyloid-ß-42 and lysozyme-C for Alzheimer's disease; peroxiredoxin-6 and α-synuclein for Parkinson's disease; kallikrein, angiotensin converting enzyme and lipocalin-1 for glaucoma; lactotransferrin and lipophilin-A for diabetic retinopathy and zinc-alpha-2 glycoprotein-1, prolactin and calcium binding protein-A4 for eye thyroid disease. We also discussed identification of tear based non-protein biomarkers like lysophospholipids and acetylcarnitine for glaucoma, 8-hydroxy-2'-deoxyquanosine and malondialdehyde for thyroid eye disease. We elucidate technological advancement in developing tear-based biosensors for diagnosis and monitoring diseases such as diabetes, diabetic retinopathy and Alzheimer's disease. Altogether, the study of tears as potential biomarkers for early diagnosis of human diseases is promising.


Subject(s)
Biomarkers, Tumor/metabolism , COVID-19 , Early Detection of Cancer , Eye Diseases , Neurodegenerative Diseases , SARS-CoV-2/metabolism , Tears/metabolism , COVID-19/diagnosis , COVID-19/metabolism , Eye Diseases/diagnosis , Eye Diseases/metabolism , Humans , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/metabolism
7.
Cancer Treat Res Commun ; 27: 100321, 2021.
Article in English | MEDLINE | ID: covidwho-1385378

ABSTRACT

BACKGROUND: ACE2 a key molecule of the Renin-Angiotensin system has been identified as the receptor for SARS-CoV-2 entry into human cells. In the context of human cancers, there is evidence that ACE2 might function as a tumor suppressor. The expression levels of ACE2 among the different subtypes of breast cancer has not been investigated. METHODS: We have examined the differential expression of ACE2 and its correlation with prognosis in breast cancer subtypes using the METABRIC (n = 1898) and TCGA (n = 832) cohorts. Correlations were evaluated by Pearsons's correlation co-efficient and Kaplan-Meier analysis was used to estimate differences in disease-free survival between the ACE2 high and ACE2 low groups. RESULTS: There is minimal expression of ACE2 in the luminal classes, but significantly higher levels in the Basal-like and HER2-enriched subclasses. Metastatic biopsies of these tumor types also show enhanced expression of ACE2. High levels of ACE2 correlated with decreased disease-free survival in the HER2-enriched subtype, and it was positively correlated with EGFR expression. CONCLUSION: These observations suggest ACE2 might function as a context dependent factor driving tumor progression in breast cancer and permit new opportunities for targeted therapy.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Receptor, ErbB-2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Multivariate Analysis , Prognosis
8.
J Mammary Gland Biol Neoplasia ; 26(3): 221-226, 2021 09.
Article in English | MEDLINE | ID: covidwho-1375665

ABSTRACT

The twelfth annual workshop of the European Network for Breast Development and Cancer focused on methods in mammary gland biology and breast cancer, was scheduled to take place on March 26-28, 2020, in Weggis, Switzerland. Due to the COVID-19 pandemic, the meeting was rescheduled twice and eventually happened as a virtual meeting on April 22 and 23, 2021. The main topics of the meeting were branching and development of the mammary gland, tumor microenvironment, circulating tumor cells, tumor dormancy and breast cancer metastasis. Novel and unpublished findings related to these topics were presented, with a particular focus on the methods used to obtain them. Virtual poster sessions were a success, with many constructive and fruitful interactions between researchers and covered many areas of mammary gland biology and breast cancer.


Subject(s)
Biomedical Research/methods , Breast Neoplasms/pathology , Mammary Glands, Human/pathology , Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Combined Modality Therapy , Europe , Female , Humans , Mammary Glands, Human/growth & development , Mammary Glands, Human/metabolism , Neoplasm Metastasis , Neoplasm Staging , Neoplastic Cells, Circulating , Prognosis , Tumor Microenvironment
9.
Aging (Albany NY) ; 13(17): 20886-20895, 2021 08 19.
Article in English | MEDLINE | ID: covidwho-1368081

ABSTRACT

The potential role of abnormal ACE2 expression after SARS-CoV-2 infection in the prognosis of breast cancer is still ambiguous. In this study, we analyzed ACE2 changes in breast cancer and studied the correlation between ACE2 and the prognosis and further analyzed the relationship between immune infiltration and the prognosis of different breast cancer subtypes. Finally, we inferred the prognosis of breast cancer patients after SARS-CoV-2 infection. We found that ACE2 expression decreased significantly in breast cancer, except for basal-like subtype. Decreased ACE2 expression level was correlated with abnormal immune infiltration and poorer prognosis of luminal B breast cancer (RFS: HR 0.76, 95%CI=0.63-0.92, p=0.005; DMFS: HR 0.70, 95%CI=0.49-1.00, p=0.046). The expression of ACE2 was strongly positively correlated with the immune infiltration level of CD8+ T cell (r=0.184, p<0.001), CD4+ T cell (r=0.104, p=0.02) and neutrophils (r=0.101, p=0.02). ACE2 expression level in the luminal subtype was positively correlated with CD8A and CD8B markers in CD8+ T cells, and CEACAM3, S100A12 in neutrophils. In conclusion, breast tumor tissues might undergo a further decrease in the expression level of ACE2 after SARS-CoV-2 infection, which could contribute to further deterioration of immune infiltration and worsen the prognosis of luminal B breast cancer after SARS-CoV-2 infection.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Breast Neoplasms/immunology , Breast Neoplasms/virology , COVID-19/enzymology , COVID-19/immunology , Lymphocytes, Tumor-Infiltrating/immunology , SARS-CoV-2/physiology , Animals , Biomarkers, Tumor/metabolism , Breast Neoplasms/enzymology , Chlorocebus aethiops , Female , Humans , Kaplan-Meier Estimate , Mice , Prognosis , Vero Cells
10.
Cancer Treat Res Commun ; 28: 100425, 2021.
Article in English | MEDLINE | ID: covidwho-1281406

ABSTRACT

BACKGROUND: Malignancy is one of the prime global causes of mortality. Cancer Patients suffering from SARS-CoV-2 have demonstrated higher rates of severe complications exacerbating towards death. Possible genetic and epigenetic alterations may exist in cancer patients which have the potential to contribute towards their increased vulnerability towards COVID-19. METHOD: An exhaustive literature search using 'COVID-19', 'SARS-CoV-2', 'Cancer', 'Malignancy', 'Relationships', Interlinks', 'Genetic', 'Epigenetic', 'Epidemiological studies', 'Clinical Studies', 'Vaccination', 'Vaccine scenario' were conducted in PubMed and EMBASE till 2nd June 2021. RESULT: In this narrative review, 17 epidemiological studies were listed which focused on clinical parameters of several malignancy patient cohorts who contracted COVID-19. Besides, genetic and epigenetic alterations seen among cancer patients are also discussed which may plausibly increase the vulnerability of cancer patients to SARS-CoV-2 infection. Also, global vaccination scenario among malignant patients along with the necessity to prioritize them in the vaccination campaigns are also elaborated. CONCLUSION: Genetic and epigenetic modifications present in ACE2, TMPRSS2, IL-6 and several cytokines require more in-depth research to elucidate the shared mechanisms of malignancy and SARS-CoV-2.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/epidemiology , COVID-19/genetics , Neoplasms/genetics , Angiotensin-Converting Enzyme 2/genetics , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Clinical Trials as Topic , Drug Carriers/administration & dosage , Epigenesis, Genetic , Genetic Predisposition to Disease , Humans , Interleukin-6/genetics , Neoplasms/epidemiology , Neoplasms/immunology , Vaccination
11.
Nat Commun ; 12(1): 3406, 2021 06 07.
Article in English | MEDLINE | ID: covidwho-1260941

ABSTRACT

Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia is associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22-2.77] adjusted for age and sex). RNAemia is comparable in performance to the best protein predictors. Mannose binding lectin 2 and pentraxin-3 (PTX3), two activators of the complement pathway of the innate immune system, are positively associated with mortality. Machine learning identified 'Age, RNAemia' and 'Age, PTX3' as the best binary signatures associated with 28-day ICU mortality. In longitudinal comparisons, COVID-19 ICU patients have a distinct proteomic trajectory associated with mortality, with recovery of many liver-derived proteins indicating survival. Finally, proteins of the complement system and galectin-3-binding protein (LGALS3BP) are identified as interaction partners of SARS-CoV-2 spike glycoprotein. LGALS3BP overexpression inhibits spike-pseudoparticle uptake and spike-induced cell-cell fusion in vitro.


Subject(s)
COVID-19/prevention & control , Critical Care/statistics & numerical data , Proteomics/methods , RNA, Viral/genetics , SARS-CoV-2/genetics , Adult , Animals , Antibodies, Neutralizing/immunology , Antigens, Neoplasm/metabolism , Biomarkers, Tumor/metabolism , C-Reactive Protein/metabolism , COVID-19/metabolism , COVID-19/virology , Female , HEK293 Cells , Humans , Kaplan-Meier Estimate , Male , Middle Aged , RNA, Viral/blood , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Serum Amyloid P-Component/metabolism , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Viral Load/immunology
12.
J Immunother Cancer ; 8(2)2020 10.
Article in English | MEDLINE | ID: covidwho-1255615

ABSTRACT

The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societies. Each of these stakeholder groups has differing interests in the use and sharing of clinical trial and biomarker data, and the conflicts caused by these differing interests represent significant obstacles to effective, widespread sharing of data. Thus, the Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to identify the current barriers to biomarker data sharing in immuno-oncology (IO) and to help in establishing professional standards for the responsible sharing of clinical trial data. The conclusions of the committee are described in two position papers: Volume I-conceptual challenges and Volume II-practical challenges, the first of which is presented in this manuscript. Additionally, the committee suggests actions by key stakeholders in the field (including organizations and professional societies) as the best path forward, encouraging the cultural shift needed to ensure responsible data sharing in the IO research setting.


Subject(s)
Biomarkers, Tumor/metabolism , Immunotherapy/methods , Information Dissemination/methods , Humans
13.
Sci Rep ; 11(1): 5228, 2021 03 04.
Article in English | MEDLINE | ID: covidwho-1117668

ABSTRACT

Clinical reports show that the management of cancer patients infected with SARS-CoV-2 requires modifications. Understanding of cancer-relevant mechanisms engaged by the virus is essential for the evidence-based management of cancer. The network of SARS-CoV-2 regulatory mechanisms was used to study potential engagement of oncogenes, tumor suppressors, other regulators of tumorigenesis and clinical markers used in the management of cancer patients. Our network analysis confirms links between COVID-19 and tumorigenesis that were predicted in epidemiological reports. The COVID-19 network shows the involvement of tumorigenesis regulators and clinical markers. Regulators of cell proliferation, death, migration, and the immune system were retrieved. Examples are pathways initiated by EGF, VEGF, TGFß and FGF. The SARS-CoV-2 network engages markers for diagnosis, prognosis and selection of treatment. Intersection with cancer diagnostic signatures supports a potential impact of the virus on tumorigenesis. Clinical observations show the diversity of symptoms correlating with biological processes and types of cells engaged by the virus, e.g. epithelial, endothelial, smooth muscle, glial and immune system cells. Our results describe an extensive engagement of cancer-relevant mechanisms and clinical markers by COVID-19. Engagement by the virus of clinical markers provides a rationale for clinical decisions based on these markers.


Subject(s)
Biomarkers, Tumor/metabolism , COVID-19/metabolism , Neoplasms/metabolism , SARS-CoV-2/metabolism , Carcinogenesis , Humans , Neoplasms/complications
14.
DNA Cell Biol ; 40(2): 359-372, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-963006

ABSTRACT

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus causing coronavirus disease 2019 (COVID-19), has been confirmed in cancers through binding specific mRNAs to invade human cells. Therefore, the aim of this study described here was to develop and validate novel SARS-CoV-2 proteins binding human mRNAs (SPBRs) signature to predict overall survival (OS) in hepatocellular carcinoma (HCC). Using multivariate Cox regression analysis, a set of SPBRs was identified to establish a multigene signature in the Cancer Genome Atlas repositories cohort. Furthermore, a nomogram was established based on the signature and clinical risk factors to improve risk stratification for individual patients. External validation was performed in the International Cancer Genome Consortium (ICGC) cohort. A six-SPBR signature was built to classify patients into two risk groups using a risk score with different OS in two cohorts (all p < 0.0001). Multivariate regression analysis demonstrated the signature was an independent predictor of HCC. Moreover, the signature presented an excellent diagnostic power in differentiating HCC and normal tissues. Gene set enrichment analysis demonstrated that high-risk group was closely enriched in cell cycle, DNA replication, microRNAs in cancer, and cytokine-cytokine receptor interaction. The novel signature demonstrated great clinical value in predicting the OS for patients with HCC, and will provide a good reference between cancer research and SARS-CoV-2 and help individualized treatment in HCC.


Subject(s)
Biomarkers, Tumor/genetics , COVID-19/complications , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/mortality , Nomograms , RNA, Messenger/genetics , SARS-CoV-2/isolation & purification , Biomarkers, Tumor/metabolism , COVID-19/transmission , COVID-19/virology , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , Cohort Studies , Female , Follow-Up Studies , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Liver Neoplasms/virology , Male , Middle Aged , Prognosis , RNA, Messenger/metabolism , Survival Rate
15.
J Am Coll Surg ; 231(4): 434-447.e2, 2020 10.
Article in English | MEDLINE | ID: covidwho-728647

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, surgical delays have been common for patients with ductal carcinoma in situ (DCIS) and early-stage estrogen receptor-positive (ER+) breast cancer, often in favor of neoadjuvant endocrine therapy (NET). To understand possible ramifications of these delays, we examined the association between time to operation and pathologic staging and overall survival (OS). STUDY DESIGN: Patients with DCIS or ER+ cT1-2N0 breast cancer treated from 2010 through 2016 were identified in the National Cancer Database. Time to operation was recorded. Factors associated with pathologic upstaging were examined using logistic regression analyses. Cox proportional hazard models were used to analyze OS. Analyses were stratified by disease stage and initial treatment strategy. RESULTS: There were 378,839 patients identified. Among those undergoing primary surgical procedure, time to operation was within 120 days in > 98% in all groups. Among cT1-2N0 patients selected for NET, operations were performed within 120 days in 59.6% of cT1N0 and 30.9% of cT2N0 patients. Increased time to operation was associated with increased odds of pathologic upstaging in DCIS patients (ER+: 60 to 120 days: odds ratio 1.15; 95% CI, 1.08 to 1.22; more than 120 days: odds ratio 1.44; 95% CI, 1.24 to 1.68; ER-: 60 to 120 days: NS; more than 120 days: odds ratio 1.36; 95% CI, 1.01 to 1.82; 60 days or less: reference), but not in patients with invasive cancer, irrespective of initial treatment strategy. No difference in OS was seen by time to operation in DCIS or NET patients. CONCLUSIONS: Increased time to operation was associated with a small increase in pathologic upstaging in DCIS patients, but did not impact OS. In patients with cT1-2N0 disease, NET use did not impact stage or OS, supporting the safety of delay strategies in ER+ breast cancer patients during the pandemic.


Subject(s)
Betacoronavirus , Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Coronavirus Infections/epidemiology , Mastectomy/methods , Neoplasm Staging , Pneumonia, Viral/epidemiology , Receptors, Estrogen/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Breast Neoplasms/epidemiology , Breast Neoplasms/surgery , COVID-19 , Carcinoma, Ductal, Breast/epidemiology , Carcinoma, Ductal, Breast/surgery , Comorbidity , Female , Follow-Up Studies , Humans , Middle Aged , Pandemics , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2 , Survival Rate/trends , Time Factors , Time-to-Treatment , United States/epidemiology , Young Adult
16.
Rev Fac Cien Med Univ Nac Cordoba ; 77(2): 117-125, 2020 06 16.
Article in Spanish | MEDLINE | ID: covidwho-617022

ABSTRACT

Introduction: The NAD+dependent proteins deacetylases are called Sirtuins (SIRT). Objectives: Objectives: this review is to study the sirtuins involved in cancer, as well as SIRT1 inhibition studies in patients with coronavirus disease COVID-19. Data source and selection: For this, a search was made in Medline, Scopus and WOS, where descriptive studies of each of the functions of sirtuins were included, adjusted to recent scientific research. SIRT1 inhibition reduces CD8 T cell cytotoxicity in patients with systemic erythematosus lupus, being susceptible to SARS Cov-2 infections. SIRT2 is regulated by the secretion of IL-4 by eosinophils and the increase in SIRT2 increases hyperplasia, in contrast, SIRT3 promotes angiogenesis, inducing cardiac remodeling. SIRT4 is a tumor suppressor, in contrastto SIRT5 that promotes cell proliferation causing colorectal cancer; SIRT6 attenuates herpes virus associated with Kaposi's Sarcoma (KSHV) in immune compromised patients. Suppression of SIRT7 inhibits the growth of endometrial cancer cells. Conclusions: It is concluded that SIRT1, SIRT2 and SIRT4 are involved in the development of cancer, the suppression of SIRT5 and SIRT7 promotes the apoptosis of cancer cells and SIRT6 attenuates the replication of KSHV, in addition to the molecular pathology pathway of COVID-19 is associated with the inhibition of SIRT1 activity that may be related to inflammatory processes.


Introducción: Las proteínas desacetilasas dependientes del NAD+, se denominan Sirtuinas (SIRT). Objetivos: estudiar las sirtuinas involucradas en el cáncer, así como los estudios de inhibición de SIRT1 en pacientes con la enfermedad del coronavirus COVID-19. Fuente y selección de datos: Para ello se realizó una búsqueda en Medline, Scopus y WOS, donde se incluyeron estudios descriptivos de cada una de las funciones de las sirtuinas ajustado a las recientes investigaciones científicas. La inhibición de SIRT1 disminuye la citotoxicidad de las células T CD8 en pacientes con lupus eritematoso sistémico, siendo susceptibles a infecciones por SARS CoV-2. La SIRT2 se regula por la secreción de IL-4 por los eosinófilos y el aumento de SIRT2 incrementa la hiperplasia, en contraste la SIRT3 promueve la angiogénesis, induciendo la remodelación cardiaca. La SIRT4 es un supresor de tumores, en contraste con la SIRT5 que promueve la proliferación celular provocando el cáncer colorrectal; la SIRT6 atenúa al herpes virus asociado al Sarcoma de Kaposi (KSHV) en pacientes inmuno comprometidos. La supresión de SIRT7 inhibe el crecimiento de las células cancerígenas endometriales. Conclusiones: Se concluye que las SIRT1, SIRT2 y SIRT4 están involucradas en el desarrollo del cáncer, la supresión de SIRT5 y SIRT7 promueve la apoptosis de células cancerígenas y la SIRT6 atenúa la replicación de KSHV, además la vía de patología molecular de la COVID-19 está asociada a la inhibición de la actividad de SIRT1 que puede estar relacionada a procesos inflamatorios.


Subject(s)
Betacoronavirus , Coronavirus Infections/metabolism , Neoplasms/metabolism , Pneumonia, Viral/metabolism , Sirtuin 1/antagonists & inhibitors , Biomarkers, Tumor/metabolism , COVID-19 , Histone Deacetylases/metabolism , Humans , Immunohistochemistry , Pandemics , SARS-CoV-2
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