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1.
Front Mol Biosci ; 7: 569414, 2020.
Article in English | MEDLINE | ID: covidwho-1793002

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) was first detected in patients with pneumonia in December 2019 in China and it spread rapidly to the rest of the world becoming a global pandemic. Several observational studies have reported that cancer is a risk factor for COVID-19. On the other hand, ACE2, a receptor for the SARS-CoV-2 virus, was found to be aberrantly expressed in many tumors. However, the characterization of aberrant ACE2 expression in malignant tumors has not been elucidated. Here, we conducted a systematic analysis of the ACE2 expression profile across 31 types of tumors. METHODS: Distribution of ACE2 expression was analyzed using the GTEx, CCLE, TCGA pan-cancer databases. We evaluated the effect of ACE2 on clinical prognosis using the Kaplan-Meier survival plot and COX regression analysis. Correlation between ACE2 and immune infiltration levels was investigated in various cancer types. Additionally, the correlation between ACE2 and immune neoantigen, TMB, microsatellite instability, Mismatch Repair Genes (MMRs), HLA gene members, and DNA Methyltransferase (DNMT) was investigated. The frequency of ACE2 gene mutation in various tumors was analyzed. Functional enrichment analysis was conducted in various cancer types using the GSEA method. RESULTS: In normal tissues, ACE2 was highly expressed in almost all 31 organs tested. In cancer cell lines, the expression level of ACE2 was low to medium. Although aberrant expression was observed in most cancer types, high expression of ACE2 was not linked to OS, DFS, RFS, and DFI in most tumors in TCGA pan-cancer data. We found that ACE2 expression was significantly correlated with the infiltrating levels of macrophages and dendritic cells, CD4+ T cells, CD8+ T cells, and B cells in multiple tumors. A positive correlation between ACE2 expression and immune neoantigen, TMB, and microsatellite instability was found in multiple cancers. GSEA analysis which was carried out to determine the effect of ACE2 on tumors indicated that several cancer-associated pathways and immune-related pathways were hyperactivated in the high ACE2 expression group of most tumors. CONCLUSION: These findings suggest that ACE2 is not correlated with prognosis in most cancer types. However, elevated ACE2 is significantly correlated with immune infiltrating levels, including those of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in multiple cancers, especially in lung and breast cancer patients. These findings suggest that ACE2 may affect the tumor environment in cancer patients with COVID-19.

2.
Eur J Neurol ; 28(10): 3418-3425, 2021 10.
Article in English | MEDLINE | ID: covidwho-1605552

ABSTRACT

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) patients could be a vulnerable group in the pandemic era of coronavirus 2019 (COVID-19) mainly due to respiratory muscle weakness, older age and long-term immunosuppressive treatment. We aimed to define factors predicting the severity of COVID-19 in MG patients and risk of MG exacerbation during COVID-19. METHODS: We evaluated clinical features and outcomes after COVID-19 in 93 MG patients. RESULTS: Thirty-five patients (38%) had severe pneumonia and we recorded 10 deaths (11%) due to COVID-19. Higher forced vital capacity (FVC) values tested before COVID-19 were shown to be protective against severe infection (95% CI 0.934-0.98) as well as good control of MG measured by the quantified myasthenia gravis score (95% CI 1.047-1.232). Long-term chronic corticosteroid treatment worsened the course of COVID-19 in MG patients (95% CI 1.784-111.43) and this impact was positively associated with dosage (p = 0.005). Treatment using azathioprine (95% CI 0.448-2.935), mycophenolate mofetil (95% CI 0.91-12.515) and ciclosporin (95% CI 0.029-2.212) did not influence the course of COVID-19. MG patients treated with rituximab had a high risk of death caused by COVID-19 (95% CI 3.216-383.971). Exacerbation of MG during infection was relatively rare (15%) and was not caused by remdesivir, convalescent plasma or favipiravir (95% CI 0.885-10.87). CONCLUSIONS: As the most important predictors of severe COVID-19 in MG patients we identified unsatisfied condition of MG with lower FVC, previous long-term corticosteroid treatment especially in higher doses, older age, the presence of cancer, and recent rituximab treatment.


Subject(s)
COVID-19 , Coronavirus Infections , Myasthenia Gravis , Aged , COVID-19/therapy , Humans , Immunization, Passive , Myasthenia Gravis/complications , Myasthenia Gravis/drug therapy , Myasthenia Gravis/epidemiology , SARS-CoV-2
3.
Int J Biol Sci ; 17(4): 1079-1087, 2021.
Article in English | MEDLINE | ID: covidwho-1524445

ABSTRACT

Fibrinogen-associated protein (FREP) family is a family of proteins with a fibrin domain at the carboxyl terminus. Recent investigations illustrated that two members of FREP family, fibrinogen-like protein-1 (FGL1) and fibrinogen-like protein-2 (FGL2), play crucial roles in cancer by regulating the proliferation, invasion, and migration of tumor cells, or regulating the functions of immune cells in tumor microenvironment. Meanwhile, they are potential targets for medical intervention of tumor development. In this review, we discussed the structure, and the roles of FGL1 and FGL2 in tumors, especially the roles in regulating immune cell functions.


Subject(s)
Fibrinogen/metabolism , Neoplasms/metabolism , Tumor Microenvironment/immunology , Animals , Humans , Immunotherapy , Molecular Targeted Therapy , Neoplasms/immunology , Neoplasms/therapy , Signal Transduction
4.
Crit Rev Biochem Mol Biol ; 56(4): 321-359, 2021 08.
Article in English | MEDLINE | ID: covidwho-1467237

ABSTRACT

CK2 is a constitutively active protein kinase that assuring a constant level of phosphorylation to its numerous substrates supports many of the most important biological functions. Nevertheless, its activity has to be controlled and adjusted in order to cope with the varying needs of a cell, and several examples of a fine-tune regulation of its activity have been described. More importantly, aberrant regulation of this enzyme may have pathological consequences, e.g. in cancer, chronic inflammation, neurodegeneration, and viral infection. Our review aims at summarizing our current knowledge about CK2 regulation. In the first part, we have considered the most important stimuli shown to affect protein kinase CK2 activity/expression. In the second part, we focus on the molecular mechanisms by which CK2 can be regulated, discussing controversial aspects and future perspectives.


Subject(s)
Casein Kinase II/metabolism , Neoplasm Proteins/metabolism , Neoplasms/enzymology , Signal Transduction , Virus Diseases/enzymology , Animals , Humans , Inflammation/enzymology
5.
Cancer Res Treat ; 53(3): 650-656, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1403959

ABSTRACT

PURPOSE: Coronavirus disease 2019 (COVID-19) pandemic has spread worldwide rapidly and patients with cancer have been considered as a vulnerable group for this infection. This study aimed to examine the expressions of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in tumor tissues of six common cancer types. MATERIALS AND METHODS: The expression levels of ACE2 and TMPRSS2 in tumors and control samples were obtained from online databases. Survival prognosis and biological functions of these genes were investigated for each tumor type. RESULTS: There was the overexpression of ACE2 in colon and stomach adenocarcinomas compared to controls, meanwhile colon and prostate adenocarcinomas showed a significantly higher expression of TMPRSS2. Additionally, survival prognosis analysis has demonstrated that upregulation of ACE2 in liver hepatocellular carcinoma was associated with higher overall survival (hazard ratio, 0.65; p=0.016) and disease-free survival (hazard ratio, 0.66; p=0.007), while overexpression of TMPRSS2 was associated with a 26% reduced risk of death in lung adenocarcinoma (p=0.047) but 50% increased risk of death in breast invasive carcinoma (p=0.015). CONCLUSION: There is a need to take extra precautions for COVID-19 in patients with colorectal cancer, stomach cancer, and lung cancer. Further information on other types of cancer at different stages should be investigated.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/diagnosis , Neoplasms/diagnosis , Neoplasms/genetics , Serine Endopeptidases/genetics , Adenocarcinoma/complications , Adenocarcinoma/diagnosis , Adenocarcinoma/epidemiology , Adenocarcinoma/genetics , Breast Neoplasms/complications , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , COVID-19/complications , COVID-19/epidemiology , COVID-19/genetics , Case-Control Studies , Databases as Topic , Female , Gastrointestinal Neoplasms/complications , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Humans , Liver Neoplasms/complications , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/genetics , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics , Male , Mutation , Neoplasms/complications , Neoplasms/epidemiology , Pandemics , Prognosis , Prostatic Neoplasms/complications , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/genetics , Retrospective Studies , SARS-CoV-2/physiology , Survival Analysis
6.
Rev Physiol Biochem Pharmacol ; 180: 1-47, 2021.
Article in English | MEDLINE | ID: covidwho-1396975

ABSTRACT

Histone deacetylases (HDACs) are a family of 18 members that participate in the epigenetic regulation of gene expression. In addition to histones, some HDACs also deacetylate transcription factors and specific cytoplasmic proteins.Monocytes, as part of the innate immune system, maintain tissue homeostasis and help fight infections and cancer. In these cells, HDACs are involved in multiple processes including proliferation, migration, differentiation, inflammatory response, infections, and tumorigenesis. Here, a systematic description of the role that most HDACs play in these functions is reviewed. Specifically, some HDACs induce a pro-inflammatory response and play major roles in host defense. Conversely, other HDACs reprogram monocytes and macrophages towards an immunosuppressive phenotype. The right balance between both types helps monocytes to respond correctly to the different physiological/pathological stimuli. However, aberrant expressions or activities of specific HDACs are associated with autoimmune diseases along with other chronic inflammatory diseases, infections, or cancer.This paper critically reviews the interesting and extensive knowledge regarding the role of some HDACs in these pathologies. It also shows that as yet, very little progress has been made toward the goal of finding effective HDAC-targeted therapies. However, given their obvious potential, we conclude that it is worth the effort to develop monocyte-specific drugs that selectively target HDAC subtypes with the aim of finding effective treatments for diseases in which our innate immune system is involved.


Subject(s)
Histone Deacetylases , Monocytes , Epigenesis, Genetic , Histone Deacetylase Inhibitors , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Histones/metabolism , Monocytes/metabolism
7.
Int J Mol Sci ; 22(9)2021 Apr 27.
Article in English | MEDLINE | ID: covidwho-1390655

ABSTRACT

The identification of thrombospondin-1 as an angiogenesis inhibitor in 1990 prompted interest in its role in cancer biology and potential as a therapeutic target. Decreased thrombospondin-1 mRNA and protein expression are associated with progression in several cancers, while expression by nonmalignant cells in the tumor microenvironment and circulating levels in cancer patients can be elevated. THBS1 is not a tumor suppressor gene, but the regulation of its expression in malignant cells by oncogenes and tumor suppressor genes mediates some of their effects on carcinogenesis, tumor progression, and metastasis. In addition to regulating angiogenesis and perfusion of the tumor vasculature, thrombospondin-1 limits antitumor immunity by CD47-dependent regulation of innate and adaptive immune cells. Conversely, thrombospondin-1 is a component of particles released by immune cells that mediate tumor cell killing. Thrombospondin-1 differentially regulates the sensitivity of malignant and nonmalignant cells to genotoxic stress caused by radiotherapy and chemotherapy. The diverse activities of thrombospondin-1 to regulate autophagy, senescence, stem cell maintenance, extracellular vesicle function, and metabolic responses to ischemic and genotoxic stress are mediated by several cell surface receptors and by regulating the functions of several secreted proteins. This review highlights progress in understanding thrombospondin-1 functions in cancer and the challenges that remain in harnessing its therapeutic potential.


Subject(s)
Neoplasms , Thrombospondin 1/physiology , Tumor Microenvironment/physiology , Animals , Cell Adhesion , Cell Movement , Humans , Integrins/metabolism , Mice , Neoplasms/blood supply , Neoplasms/immunology , Neoplasms/pathology , Neovascularization, Pathologic/metabolism , Neovascularization, Physiologic/genetics , T-Lymphocytes/immunology , Thrombospondin 1/genetics , Thrombospondin 1/metabolism
8.
Int J Mol Sci ; 22(3)2021 Jan 22.
Article in English | MEDLINE | ID: covidwho-1389387

ABSTRACT

In this review, we discuss the major histocompatibility complex (MHC) class II transactivator (CIITA), which is the master regulator of MHC class II gene expression. CIITA is the founding member of the mammalian nucleotide-binding and leucine-rich-repeat (NLR) protein family but stood apart for a long time as the only transcriptional regulator. More recently, it was found that its closest homolog, NLRC5 (NLR protein caspase activation and recruitment domain (CARD)-containing 5), is a regulator of MHC-I gene expression. Both act as non-DNA-binding activators through multiple protein-protein interactions with an MHC enhanceosome complex that binds cooperatively to a highly conserved combinatorial cis-acting module. Thus, the regulation of MHC-II expression is regulated largely through the differential expression of CIITA. In addition to the well-defined role of CIITA in MHC-II GENE regulation, we will discuss several other aspects of CIITA functions, such as its role in cancer, its role as a viral restriction element contributing to intrinsic immunity, and lastly, its very recently discovered role as an inhibitor of Ebola and SARS-Cov-2 virus replication. We will briefly touch upon the recently discovered role of NLRP3 as a transcriptional regulator, which suggests that transcriptional regulation is, after all, not such an unusual feature for NLR proteins.


Subject(s)
Genes, MHC Class II , NLR Proteins/metabolism , Nuclear Proteins/metabolism , Trans-Activators/metabolism , Animals , COVID-19/genetics , COVID-19/metabolism , Ebolavirus/physiology , Gene Expression Regulation , Hemorrhagic Fever, Ebola/genetics , Hemorrhagic Fever, Ebola/metabolism , Humans , NLR Proteins/genetics , Neoplasms/genetics , Neoplasms/metabolism , Nuclear Proteins/genetics , Protein Interaction Maps , SARS-CoV-2/physiology , Trans-Activators/genetics , Virus Replication
9.
Clin Cancer Res ; 27(16): 4468-4477, 2021 08 15.
Article in English | MEDLINE | ID: covidwho-1379685

ABSTRACT

Among the hallmarks of cancer is the ability of neoplastic cells to evade and suppress immune surveillance to allow their growth and evolution. Nowhere is this as apparent as in multiple myeloma, a cancer of antibody-producing plasma cells, where a complex interplay between neoplastic cells and the immune microenvironment is required for the development and progression of disease. Decades of research has led to the discovery of a number of therapeutic agents, from cytotoxic drugs to genetically engineered cells that mediate their antimyeloma effects at least partially through altering these immune interactions. In this review, we discuss the history of immunotherapy and current practices in multiple myeloma, as well as the advances that promise to one day offer a cure for this deadly disease.


Subject(s)
Immunotherapy , Multiple Myeloma/therapy , Humans , Multiple Myeloma/immunology
11.
Int J Radiat Oncol Biol Phys ; 110(2): 272-273, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1343244
12.
Med Sci Monit ; 27: e933088, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1314975

ABSTRACT

Synthetic mRNA and the expression of therapeutic proteins have accelerated vaccine development to prevent infection and heralds a new era in targeted immunotherapy in oncology. Therapeutic mRNA vaccines rely on available tumor tissue for gene sequencing analysis to compare the patient's normal cellular DNA sequences and those of the tumor. Carrier-based mRNA vaccines for cancer immunotherapy are now in development that use delivery systems based on peptides, lipids, polymers, and cationic nano-emulsions. There have also been recent developments in dendritic cell-based mRNA vaccines. For patients with available tumor tissue samples, it is possible to develop mRNA vaccines that result in the expression of tumor antigens by antigen-presenting cells (APCs), resulting in innate and adaptive immune responses. Ongoing developments in mRNA immunotherapy include modifications in the route of administration and combined delivery of multiple mRNA vaccines with checkpoint inhibitors. This Editorial aims to present a brief overview of how mRNA immunotherapy may change the therapeutic landscape of personalized medicine for patients with solid malignant tumors.


Subject(s)
Cancer Vaccines/immunology , Neoplasms/immunology , Neoplasms/therapy , RNA, Messenger/immunology , Vaccines, Synthetic/immunology , Humans , Immunotherapy/methods , Medical Oncology/methods , Precision Medicine/methods
13.
Cancers (Basel) ; 13(7)2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1295765

ABSTRACT

Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SNPs) in DPP9 and loss of function (LoF) variants have not been explored. Human genomic databases, including The Cancer Genome Atlas (TCGA), were interrogated to identify DPP9 LoF variants and associated cancers. Survival and gene signature analyses were performed on hepatocellular carcinoma (HCC) data. We found that DPP9 and DPP8 are intolerant to LoF variants. DPP9 exonic LoF variants were most often associated with uterine carcinoma and lung carcinoma. All four DPP4-like genes were overexpressed in liver tumors and their joint high expression was associated with poor survival in HCC. Increased DPP9 expression was associated with obesity in HCC patients. High expression of genes that positively correlated with overexpression of DPP4, DPP8, and DPP9 were associated with very poor survival in HCC. Enriched pathways analysis of these positively correlated genes featured Toll-like receptor and SUMOylation pathways. This comprehensive data mining suggests that DPP9 is important for survival and that the DPP4 protease family, particularly DPP9, is important in the pathogenesis of human HCC.

14.
FEBS Open Bio ; 2021 Jun 17.
Article in English | MEDLINE | ID: covidwho-1274656

ABSTRACT

Cancer cell dysregulations result in the abnormal regulation of cellular metabolic pathways. By simulating this metabolic reprogramming using constraint-based modeling approaches, oncogenes can be predicted, and this knowledge can be used in prognosis and treatment. We introduced a trilevel optimization problem describing metabolic reprogramming for inferring oncogenes. First, this study used RNA-Seq expression data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) samples and their healthy counterparts to reconstruct tissue-specific genome-scale metabolic models and subsequently build the flux distribution pattern that provided a measure for the oncogene inference optimization problem for determining tumorigenesis. The platform detected 45 genes for LUAD and 84 genes for LUSC that lead to tumorigenesis. A high level of differentially expressed genes was not an essential factor for determining tumorigenesis. The platform indicated that pyruvate kinase (PKM), a well-known oncogene with a low level of differential gene expression in LUAD and LUSC, had the highest fitness among the predicted oncogenes based on computation. By contrast, pyruvate kinase L/R (PKLR), an isozyme of PKM, had a high level of differential gene expression in both cancers. Phosphatidylserine synthase 1 (PTDSS1), an oncogene in LUAD, was inferred to have a low level of differential gene expression, and overexpression could significantly reduce survival probability. According to the factor analysis, PTDSS1 characteristics were close to those of the template, but they were unobvious in LUSC. Angiotensin-converting enzyme 2 (ACE2) has recently garnered widespread interest as the SARS-CoV-2 virus receptor. Moreover, we determined that ACE2 is an oncogene of LUSC but not of LUAD. The platform developed in this study can identify oncogenes with low levels of differential expression and be used to identify potential therapeutic targets for cancer treatment.

15.
Proc Jpn Acad Ser B Phys Biol Sci ; 97(6): 277-291, 2021.
Article in English | MEDLINE | ID: covidwho-1267427

ABSTRACT

Cytokines are important intercellular communication tools for immunity. Most cytokines utilize the JAK-STAT and Ras-ERK pathways to promote gene transcription and proliferation; however, this signaling is tightly regulated. The suppressor of cytokine signaling (SOCS) family and SPRED family are a representative negative regulators of the JAK-STAT pathway and the Ras-ERK pathway, respectively. The SOCS family regulates the differentiation and function of CD4+ T cells, CD8+ T cells, and regulatory T cells, and is involved in immune tolerance, anergy, and exhaustion. SPRED family proteins have been shown to inactivate Ras by recruiting the Ras-GTPase neurofibromatosis type 1 (NF1) protein. Human genetic analysis has shown that SOCS family members are strongly associated with autoimmune diseases, allergies, and tumorigenesis, and SPRED1 is involved in NF1-like syndromes and tumors. We also identified the NR4a family of nuclear receptors as a key transcription factor for immune tolerance that suppresses cytokine expression and induces various immuno-regulatory molecules including SOCS1.


Subject(s)
CD8-Positive T-Lymphocytes , Suppressor of Cytokine Signaling Proteins , CD8-Positive T-Lymphocytes/metabolism , Cytokines/metabolism , Humans , Immune Tolerance , Signal Transduction , Suppressor of Cytokine Signaling Proteins/metabolism
16.
Int J Biol Sci ; 17(8): 1925-1939, 2021.
Article in English | MEDLINE | ID: covidwho-1266906

ABSTRACT

Background: Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) allow entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells and play essential roles in cancer therapy. However, the functions of ACE2 and TMPRSS2 in kidney cancer remain unclear, especially as kidneys are targets for SARS-CoV-2 infection. Methods: UCSC Xena project, the Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases (GSE30589 and GSE59185) were searched for gene expression in human tissues, gene expression data, and clinical information. Several bioinformatics methods were utilized to analyze the correlation between ACE2 and TMPRSS2 with respect to the prognosis of kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP). Results: ACE2 expression was significantly upregulated in tumor tissue, while its downregulation was associated with low survival in KIRC and KIRP patients. TMPRSS2 was downregulated in KIRC and KIRP, and its expression was not correlated with patient survival. According to clinical risk factor-based prediction models, ACE2 exhibits predictive accuracy for kidney cancer prognosis and is correlated with metabolism and immune infiltration. In an animal model, ACE2 expression was remarkably downregulated in SARS-CoV-2-infected cells compared to in the control. Conclusion: ACE2 expression is highly correlated with various metabolic pathways and is involved in immune infiltration.it plays a crucial role than TMPRSS2 in diagnosing and prognosis of kidney cancer patients. The overlap in ACE2 expression between kidney cancer and SARS-CoV-2 infection suggests that patients with KIRC or KIRP are at high risk of developing serious symptoms.


Subject(s)
Angiotensin-Converting Enzyme 2/biosynthesis , COVID-19/complications , Carcinoma, Renal Cell/complications , Kidney Neoplasms/complications , Receptors, Virus/biosynthesis , SARS-CoV-2 , Adult , Aged , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/physiology , Animals , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/mortality , Chlorocebus aethiops , Down-Regulation , Drug Resistance, Neoplasm , Female , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/immunology , Kidney Neoplasms/metabolism , Kidney Neoplasms/mortality , Lymphocytes, Tumor-Infiltrating/immunology , Male , Middle Aged , Models, Animal , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Organ Specificity , Prognosis , Proportional Hazards Models , Receptors, Virus/genetics , Renin-Angiotensin System/physiology , Serine Endopeptidases/biosynthesis , Serine Endopeptidases/genetics , Serine Endopeptidases/physiology , Tissue Array Analysis , Vero Cells
17.
Front Mol Biosci ; 8: 666054, 2021.
Article in English | MEDLINE | ID: covidwho-1264344

ABSTRACT

The novel coronavirus pneumonia COVID-19 is characterized by all age susceptibility, which imposes a dramatic threat to the human species all over the world. According to current available data, the cytokine storm appears to be the most life-threatening symptom of severe COVID-19 cases accompanied with lung fibrosis. Galectin-3 (Gal-3), a member of soluble ß-galactoside-binding lectin families, has been implicated as a key regulator in various inflammation conditions in addition to its well-documented roles in cancer. The pro-inflammatory activity of Gal-3 in the inflammatory response and lung fibrosis of COVID-19 has been proposed by emerging studies, which suggested that inhibition of Gal-3 may represent a novel treatment approach for COVID-19 patients. Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with poor prognosis. ICC accounts for 10-25% of primary liver cancers with limited therapeutic options, which has higher incidence in Asian countries, particularly in China. Cancer patients, including ICC patients, are highly vulnerable to COVID-19 due to their impaired immune system. It is thus undoubtedly a challenge for our oncology department to establish effective treatment strategies under the influence of the COVID-19 crisis. According to our management procedures in the COVID-19 era, emergency treatment will be applied to ICC patients who are under life-threatening conditions, despite the COVID-19 infection. To the best of our knowledge, the modulatory function of Gal-3 in ICC is still barely explored to date. In order to evaluate the therapeutic potential of Gal-3 for ICC patients or those comprised with COVID-19, we herein report our preliminary investigation into roles of Gal-3 in ICC. Our results exhibited that the expression of Gal-3 was significantly up-regulated in ICC tissues, and a significant correlation was observed between its overexpression and malignant progression of ICC cells. We further discussed the activity and possible molecular mechanisms of Gal-3 in ICC, which may pave the ways for further exploring the possibility of Gal-3 as a potential therapeutic target for treating ICC patients or those with COVID-19-related conditions.

18.
J Med Internet Res ; 23(6): e24947, 2021 06 09.
Article in English | MEDLINE | ID: covidwho-1262582

ABSTRACT

BACKGROUND: Telehealth is an increasingly important component of health care delivery in response to the COVID-19 pandemic. However, well-documented disparities persist in the use of digital technologies. OBJECTIVE: This study aims to describe smartphone and internet use within a diverse sample, to assess the association of smartphone and internet use with markers of health literacy and health access, and to identify the mediating factors in these relationships. METHODS: Surveys were distributed to a targeted sample designed to oversample historically underserved communities from April 2017 to December 2017. Multivariate logistic regression was used to estimate the association of internet and smartphone use with outcomes describing health care access and markers of health literacy for the total cohort and after stratifying by personal history of cancer. Health care access was captured using multiple variables, including the ability to obtain medical care when needed. Markers of health literacy included self-reported confidence in obtaining health information. RESULTS: Of the 2149 participants, 1319 (61.38%) were women, 655 (30.48%) were non-Hispanic White, and 666 (30.99%) were non-Hispanic Black. The median age was 51 years (IQR 38-65). Most respondents reported using the internet (1921/2149, 89.39%) and owning a smartphone (1800/2149, 83.76%). Compared with the respondents with smartphone or internet access, those without smartphone or internet access were more likely to report that a doctor was their most recent source of health information (344/1800, 19.11% vs 116/349, 33.2% for smartphone and 380/1921, 19.78% vs 80/228, 35.1% for internet, respectively; both P<.001). Internet use was associated with having looked for information on health topics from any source (odds ratio [OR] 3.81, 95% CI 2.53-5.75) and confidence in obtaining health information when needed (OR 1.83, 95% CI 1.00-3.34) compared with noninternet users. Smartphone owners had lower odds of being unable to obtain needed medical care (OR 0.62, 95% CI 0.40-0.95) than nonsmartphone owners. Among participants with a prior history of cancer, smartphone ownership was significantly associated with higher odds of confidence in ability to obtain needed health information (OR 5.63, 95% CI 1.05-30.23) and lower odds of inability to obtain needed medical care (OR 0.17, 95% CI 0.06-0.47), although these associations were not significant among participants without a prior history of cancer. CONCLUSIONS: We describe widespread use of digital technologies in a community-based cohort, although disparities persist. In this cohort, smartphone ownership was significantly associated with ability to obtain needed medical care, suggesting that the use of smartphone technology may play a role in increasing health care access. Similarly, major illnesses such as cancer have the potential to amplify health engagement. Finally, special emphasis must be placed on reaching patient populations with limited digital access, so these patients are not further disadvantaged in the new age of telehealth.


Subject(s)
Health Literacy/statistics & numerical data , Health Services Accessibility , Internet Use/statistics & numerical data , Neoplasms/prevention & control , Ownership , Smartphone/statistics & numerical data , Surveys and Questionnaires , Telemedicine/statistics & numerical data , Adult , Aged , Cohort Studies , Cross-Sectional Studies , Female , Humans , Internet , Male , Middle Aged , Self Report , Smartphone/supply & distribution , Vulnerable Populations
19.
J Pathol ; 254(4): 303-306, 2021 07.
Article in English | MEDLINE | ID: covidwho-1258101

ABSTRACT

The 2021 Annual Review Issue of The Journal of Pathology contains 14 invited reviews on current research areas of particular importance in pathology. The subjects included here reflect the broad range of interests covered by the journal, including both basic and applied research fields but always with the aim of improving our understanding of human disease. This year, our reviews encompass the huge impact of the COVID-19 pandemic, the development and application of biomarkers for immune checkpoint inhibitors, recent advances in multiplexing antigen/nucleic acid detection in situ, the use of genomics to aid drug discovery, organoid methodologies in research, the microbiome in cancer, the role of macrophage-stroma interactions in fibrosis, and TGF-ß as a driver of fibrosis in multiple pathologies. Other reviews revisit the p53 field and its lack of clinical impact to date, dissect the genetics of mitochondrial diseases, summarise the cells of origin and genetics of sarcomagenesis, provide new data on the role of TRIM28 in tumour predisposition, review our current understanding of cancer stem cell niches, and the function and regulation of p63. The reviews are authored by experts in their field from academia and industry, and provide comprehensive updates of the chosen areas, in which there has been considerable recent progress. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Subject(s)
COVID-19/genetics , COVID-19/virology , Neoplasms/pathology , SARS-CoV-2/pathogenicity , COVID-19/pathology , Genomics/methods , Humans , Neoplasms/complications , Neoplasms/genetics , Organoids/pathology , United Kingdom
20.
JAMA Oncol ; 7(8): 1141-1148, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1245334

ABSTRACT

Importance: Patients with cancer and health care workers (HCWs) are at high risk of SARS-CoV-2 infection. Assessing the antibody status of patients with cancer and HCWs can help understand the spread of COVID-19 in cancer care. Objective: To evaluate serum SARS-CoV-2 antibody status in patients with cancer and HCWs during the COVID-19 pandemic in Japan. Design, Setting, and Participants: Participants were enrolled for this prospective cross-sectional study between August 3 and October 30, 2020, from 2 comprehensive cancer centers in the epidemic area around Tokyo, Japan. Patients with cancer aged 16 years or older and employees were enrolled. Participants with suspected COVID-19 infection at the time of enrollment were excluded. Exposures: Cancer of any type and cancer treatment, including chemotherapy, surgery, immune checkpoint inhibitors, radiotherapy, and targeted molecular therapy. Main Outcomes and Measures: Seroprevalence and antibody levels in patients with cancer and HCWs. Seropositivity was defined as positivity to nucleocapsid IgG (N-IgG) and/or spike IgG (S-IgG). Serum levels of SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured by chemiluminescent enzyme immunoassay. Results: A total of 500 patients with cancer (median age, 62.5 years [range, 21-88 years]; 265 men [55.4%]) and 1190 HCWs (median age, 40 years [range, 20-70 years]; 382 men [25.4%]) were enrolled. In patients with cancer, 489 (97.8%) had solid tumors, and 355 (71.0%) had received anticancer treatment within 1 month. Among HCWs, 385 (32.3%) were nurses or assistant nurses, 266 (22.4%) were administrative officers, 197 (16.6%) were researchers, 179 (15.0%) were physicians, 113 (9.5%) were technicians, and 50 (4.2%) were pharmacists. The seroprevalence was 1.0% (95% CI, 0.33%-2.32%) in patients and 0.67% (95% CI, 0.29%-1.32%) in HCWs (P = .48). However, the N-IgG and S-IgG antibody levels were significantly lower in patients than in HCWs (N-IgG: ß, -0.38; 95% CI, -0.55 to -0.21; P < .001; and S-IgG: ß, -0.39; 95% CI, -0.54 to -0.23; P < .001). Additionally, among patients, N-IgG levels were significantly lower in those who received chemotherapy than in those who did not (median N-IgG levels, 0.1 [interquartile range (IQR), 0-0.3] vs 0.1 [IQR, 0-0.4], P = .04). In contrast, N-IgG and S-IgG levels were significantly higher in patients who received immune checkpoint inhibitors than in those who did not (median N-IgG levels: 0.2 [IQR, 0.1-0.5] vs 0.1 [IQR, 0-0.3], P = .02; S-IgG levels: 0.15 [IQR, 0-0.3] vs 0.1[IQR, 0-0.2], P = .02). Conclusions and Relevance: In this cross-sectional study of Japanese patients with cancer and HCWs, the seroprevalence of SARS-CoV-2 antibodies did not differ between the 2 groups; however, findings suggest that comorbid cancer and treatment with systemic therapy, including chemotherapy and immune checkpoint inhibitors, may influence the immune response to SARS-CoV-2.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Neoplasms/immunology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , COVID-19/blood , Cross-Sectional Studies , Female , Health Personnel , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Japan , Male , Middle Aged , Neoplasms/blood , Pandemics/prevention & control , Prospective Studies , Young Adult
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