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1.
PLoS One ; 16(8): e0256544, 2021.
Article in English | MEDLINE | ID: covidwho-1374151

ABSTRACT

BACKGROUND: Patients with hepatocellular carcinoma (HCC) represent a vulnerable population potentially negatively affected by COVID-19-associated reallocation of healthcare resources. Here, we report the impact of COVID-19 on the management of HCC patients in a large tertiary care hospital. METHODS: We retrospectively analyzed clinical data of HCC patients who presented at the Vienna General Hospital, between 01/DEC/2019 and 30/JUN/2020. We compared patient care before (period 1) and after (period 2) implementation of COVID-19-associated healthcare restrictions on 16/MAR/2020. RESULTS: Of 126 patients, majority was male (n = 104, 83%) with a mean age of 66±11 years. Half of patients (n = 57, 45%) had impaired liver function (Child-Pugh stage B/C) and 91 (72%) had intermediate-advanced stage HCC (BCLC B-D). New treatment, was initiated in 68 (54%) patients. Number of new HCC diagnoses did not differ between the two periods (n = 14 vs. 14). While personal visits were reduced, an increase in teleconsultation was observed (period 2). Number of patients with visit delays (n = 31 (30%) vs. n = 10 (10%); p = 0.001) and imaging delays (n = 25 (25%) vs. n = 7 (7%); p = 0.001) was higher in period 2. Accordingly, a reduced number of patients was discussed in interdisciplinary tumor boards (lowest number in April (n = 24), compared to a median number of 57 patients during period 1). Median number of elective/non-elective admissions was not different between the periods. One patient contracted COVID-19 with lethal outcome. CONCLUSIONS: Changes in patient care included reduced personal contacts but increased telephone visits, and delays in diagnostic procedures. The effects on long-term outcome need to be determined.


Subject(s)
COVID-19/epidemiology , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , COVID-19/virology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Delayed Diagnosis , Female , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Pandemics , Patients/psychology , Retrospective Studies , SARS-CoV-2/isolation & purification , Survival Rate , Telemedicine , Tertiary Care Centers
2.
Bioengineered ; 12(1): 4054-4069, 2021 12.
Article in English | MEDLINE | ID: covidwho-1348035

ABSTRACT

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Carcinoma, Hepatocellular/genetics , Liver Cirrhosis/genetics , Liver Neoplasms/genetics , Neoplasm Proteins/genetics , Receptors, Virus/genetics , alpha-Fetoproteins/genetics , Age Factors , Aged , Angiotensin-Converting Enzyme 2/metabolism , Area Under Curve , COVID-19/virology , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Databases, Genetic , Datasets as Topic , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/mortality , Liver Cirrhosis/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Proteins/classification , Neoplasm Proteins/metabolism , Protective Factors , Protein Interaction Mapping , ROC Curve , Receptors, Virus/metabolism , SARS-CoV-2/pathogenicity , Survival Analysis , alpha-Fetoproteins/metabolism
3.
Neuropeptides ; 89: 102159, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1225350

ABSTRACT

T cells of aged people, and of patients with either cancer or severe infections (including COVID-19), are often exhausted, senescent and dysfunctional, leading to increased susceptibilities, complications and mortality. Neurotransmitters and Neuropeptides bind their receptors in T cells, and induce multiple beneficial T cell functions. Yet, T cells of different people vary in the expression levels of Neurotransmitter and Neuropeptide receptors, and in the magnitude of the corresponding effects. Therefore, we performed an individual-based study on T cells of 3 healthy subjects, and 3 Hepatocellular Carcinoma (HCC) patients. HCC usually develops due to chronic inflammation. The inflamed liver induces reduction and inhibition of CD4+ T cells and Natural Killer (NK) cells. Immune-based therapies for HCC are urgently needed. We tested if selected Neurotransmitters and Neuropeptides decrease the key checkpoint protein PD-1 in human T cells, and increase proliferation and killing of HCC cells. First, we confirmed human T cells express all dopamine receptors (DRs), and glutamate receptors (GluRs): AMPA-GluR3, NMDA-R and mGluR. Second, we discovered that either Dopamine, Glutamate, GnRH-II, Neuropeptide Y and/or CGRP (10nM), as well as DR and GluR agonists, induced the following effects: 1. Decreased significantly both %PD-1+ T cells and PD-1 expression level per cell (up to 60% decrease, within 1 h only); 2. Increased significantly the number of T cells that proliferated in the presence of HCC cells (up to 7 fold increase), 3. Increased significantly T cell killing of HCC cells (up to 2 fold increase). 4. Few non-conventional combinations of Neurotransmitters and Neuropeptides had surprising synergistic beneficial effects. We conclude that Dopamine, Glutamate, GnRH-II, Neuropeptide Y and CGRP, alone or in combinations, can decrease % PD-1+ T cells and PD-1 expression per cell, in T cells of both healthy subjects and HCC patients, and increase their proliferation in response to HCC cells and killing of HCC cells. Yet, testing T cells of many more cancer patients is absolutely needed. Based on these findings and previous ones, we designed a novel "Personalized Adoptive Neuro-Immunotherapy", calling for validation of safety and efficacy in clinical trials.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Cell Proliferation/drug effects , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Neuropeptides/pharmacology , Neurotransmitter Agents/pharmacology , Programmed Cell Death 1 Receptor/biosynthesis , Programmed Cell Death 1 Receptor/genetics , T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/metabolism , COVID-19/complications , Carcinoma, Hepatocellular/pathology , Dopamine/pharmacology , Dopamine Agonists/pharmacology , Humans , Immunotherapy , Killer Cells, Natural/metabolism , Liver Neoplasms/pathology , Receptors, Glutamate/drug effects , Receptors, Neuropeptide/metabolism , Receptors, Neurotransmitter/metabolism
6.
Lancet Gastroenterol Hepatol ; 5(8): 765-775, 2020 08.
Article in English | MEDLINE | ID: covidwho-692971

ABSTRACT

Around the world, recommendations for cancer treatment are being adapted in real time in response to the pandemic of COVID-19. We, as a multidisciplinary team, reviewed the standard management options, according to the Barcelona Clinic Liver Cancer classification system, for hepatocellular carcinoma. We propose treatment recommendations related to COVID-19 for the different stages of hepatocellular carcinoma (ie, 0, A, B, and C), specifically in relation to surgery, locoregional therapies, and systemic therapy. We suggest potential strategies to modify risk during the pandemic and aid multidisciplinary treatment decision making. We also review the multidisciplinary management of intrahepatic cholangiocarcinoma as a potentially curable and incurable diagnosis in the setting of COVID-19.


Subject(s)
Carcinoma, Hepatocellular/therapy , Coronavirus Infections/epidemiology , Liver Neoplasms/therapy , Pandemics , Pneumonia, Viral/epidemiology , Betacoronavirus , Bile Duct Neoplasms/therapy , COVID-19 , Carcinoma, Hepatocellular/pathology , Cholangiocarcinoma/therapy , Clinical Decision-Making , Humans , Liver Neoplasms/pathology , Neoplasm Staging , Patient Care Team , Risk Factors , SARS-CoV-2
9.
Mol Biol Rep ; 47(6): 4383-4392, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-260333

ABSTRACT

The ACE2 gene is a receptor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) for COVID-19 (coronavirus disease 2019). To analyze the expression profiles and clinical significances for this gene in humans, RNA-seq data representing 27 different tissues were analyzed using NCBI; total RNA was extracted from different tissues of mouse and semi-quantitative reverse transcriptional-polymerase chain reaction (Q-RT-PCR) was carried out. Immunohistochemistry expression profiles in normal tissues and cancer tissues and TCGA survival analysis in renal and liver cancer were conducted. ACE2 was highly conserved in different species. In normal tissues, ACE2 expression distributions were organ-specific, mainly in the kidney, male testis and female breast, and cardiovascular and gastrointestinal systems. High level of expression in testis, cardiovascular and gastrointestinal system indicated that SARS-CoV-2 might not only attack the lungs, but also affect other organs, particularly the testes, thus it may severely damage male sexual development for younger male and lead to infertility in an adult male, if he contracted COVID-19. On the other side, high expression of ACE2 was correlated with increased survival rate in renal and liver cancer, indicating that ACE2 is a prognostic marker in both renal cancer and liver cancers. Thus, the ACE2 is a functional receptor for SARS-CoV-2 and has a potential anti-tumor role in cancer. Taken together, this study may not only provide potential clues for further medical pathogenesis of COVID-19 and male fertility, but also indicate the clinical significance of the role of the ACE2 gene in cancer.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Kidney Neoplasms/genetics , Liver Neoplasms/genetics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/epidemiology , Receptors, Virus/genetics , Spike Glycoprotein, Coronavirus/genetics , Adult , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/drug effects , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/genetics , Databases, Genetic , Female , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Humans , Kidney/metabolism , Kidney/pathology , Kidney/virology , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Kidney Neoplasms/virology , Liver/metabolism , Liver/pathology , Liver/virology , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/virology , Lung/metabolism , Lung/pathology , Lung/virology , Male , Mammary Glands, Human/metabolism , Mammary Glands, Human/pathology , Mammary Glands, Human/virology , Mice , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/genetics , Protein Binding , Receptors, Virus/metabolism , SARS-CoV-2 , Sequence Analysis, RNA , Signal Transduction , Spike Glycoprotein, Coronavirus/metabolism , Survival Analysis , Testis/metabolism , Testis/pathology , Testis/virology
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