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1.
Cancer Invest ; 40(5): 401-405, 2022 May.
Article in English | MEDLINE | ID: covidwho-1778718

ABSTRACT

The study is to evaluate the impact of COVID-19 in the Pediatric Oncology Units (POUs) of Pakistan. Data from 1 April 2019 to 30 June 2019 and 1 April 2020 to 30 June 2020 for the first and second cohort, respectively, in order to compare the registration, abandonment rate, and delay in treatment. Six hundred and thirty-four were registered cases, 379 and 255 in the first and second cohort, respectively, which was significantly different <0.005. Seventy-seven were abandoned, 45 and 32 in the first and second cohort, respectively. Fifty-nine COVID-19 positive cases, 24, 4, 27, and 4 were admitted, referred, home isolated, and leave against medical advice (LAMA), respectively. Delayed treatment and reduction in new cases were observed.


Subject(s)
COVID-19 , Neoplasms , Child , Hospitalization , Humans , Neoplasms/epidemiology , Neoplasms/therapy , Pakistan/epidemiology , SARS-CoV-2
2.
J Med Internet Res ; 23(2): e24767, 2021 02 22.
Article in English | MEDLINE | ID: covidwho-1575466

ABSTRACT

BACKGROUND: Online medical records are being used to organize processes in clinical and outpatient settings and to forge doctor-patient communication techniques that build mutual understanding and trust. OBJECTIVE: We aimed to understand the reasons why patients tend to avoid using online medical records and to compare the perceptions that patients have of online medical records based on demographics and cancer diagnosis. METHODS: We used data from the Health Information National Trends Survey Cycle 3, a nationally representative survey, and assessed outcomes using descriptive statistics and chi-square tests. The patients (N=4328) included in the analysis had experienced an outpatient visit within the previous 12 months and had answered the online behavior question regarding their use of online medical records. RESULTS: Patients who were nonusers of online medical records consisted of 58.36% of the sample (2526/4328). The highest nonuser rates were for patients who were Hispanic (460/683, 67.35%), patients who were non-Hispanic Black (434/653, 66.46%), and patients who were older than 65 years (968/1520, 63.6%). Patients older than 65 years were less likely to use online medical records (odds ratio [OR] 1.51, 95% CI 1.24-1.84, P<.001). Patients who were White were more likely to use online medical records than patients who were Black (OR 1.71, 95% CI 1.43-2.05, P<.001) or Hispanic (OR 1.65, 95% CI 1.37-1.98, P<.001). Patients who were diagnosed with cancer were more likely to use online medical records compared to patients with no cancer (OR 1.31, 95% CI 1.11-1.55, 95% CI 1.11-1.55, P=.001). Among nonusers, older patients (≥65 years old) preferred speaking directly to their health care providers (OR 1.76, 95% CI 1.35-2.31, P<.001), were more concerned about privacy issues caused by online medical records (OR 1.79, 95% CI 1.22-2.66, P<.001), and felt uncomfortable using the online medical record systems (OR 10.55, 95% CI 6.06-19.89, P<.001) compared to those aged 18-34 years. Patients who were Black or Hispanic were more concerned about privacy issues (OR 1.42, 1.09-1.84, P=.007). CONCLUSIONS: Studies should consider social factors such as gender, race/ethnicity, and age when monitoring trends in eHealth use to ensure that eHealth use does not induce greater health status and health care disparities between people with different backgrounds and demographic characteristics.


Subject(s)
Electronic Health Records/standards , Health Information Exchange/standards , Surveys and Questionnaires/standards , Adolescent , Adult , Aged , Data Analysis , Female , History, 21st Century , Humans , Internet Use , Male , Middle Aged , Physician-Patient Relations , Telemedicine/statistics & numerical data , Young Adult
3.
Lancet Oncol ; 22(6): 765-778, 2021 06.
Article in English | MEDLINE | ID: covidwho-1531901

ABSTRACT

BACKGROUND: The efficacy and safety profiles of vaccines against SARS-CoV-2 in patients with cancer is unknown. We aimed to assess the safety and immunogenicity of the BNT162b2 (Pfizer-BioNTech) vaccine in patients with cancer. METHODS: For this prospective observational study, we recruited patients with cancer and healthy controls (mostly health-care workers) from three London hospitals between Dec 8, 2020, and Feb 18, 2021. Participants who were vaccinated between Dec 8 and Dec 29, 2020, received two 30 µg doses of BNT162b2 administered intramuscularly 21 days apart; patients vaccinated after this date received only one 30 µg dose with a planned follow-up boost at 12 weeks. Blood samples were taken before vaccination and at 3 weeks and 5 weeks after the first vaccination. Where possible, serial nasopharyngeal real-time RT-PCR (rRT-PCR) swab tests were done every 10 days or in cases of symptomatic COVID-19. The coprimary endpoints were seroconversion to SARS-CoV-2 spike (S) protein in patients with cancer following the first vaccination with the BNT162b2 vaccine and the effect of vaccine boosting after 21 days on seroconversion. All participants with available data were included in the safety and immunogenicity analyses. Ongoing follow-up is underway for further blood sampling after the delayed (12-week) vaccine boost. This study is registered with the NHS Health Research Authority and Health and Care Research Wales (REC ID 20/HRA/2031). FINDINGS: 151 patients with cancer (95 patients with solid cancer and 56 patients with haematological cancer) and 54 healthy controls were enrolled. For this interim data analysis of the safety and immunogenicity of vaccinated patients with cancer, samples and data obtained up to March 19, 2021, were analysed. After exclusion of 17 patients who had been exposed to SARS-CoV-2 (detected by either antibody seroconversion or a positive rRT-PCR COVID-19 swab test) from the immunogenicity analysis, the proportion of positive anti-S IgG titres at approximately 21 days following a single vaccine inoculum across the three cohorts were 32 (94%; 95% CI 81-98) of 34 healthy controls; 21 (38%; 26-51) of 56 patients with solid cancer, and eight (18%; 10-32) of 44 patients with haematological cancer. 16 healthy controls, 25 patients with solid cancer, and six patients with haematological cancer received a second dose on day 21. Of the patients with available blood samples 2 weeks following a 21-day vaccine boost, and excluding 17 participants with evidence of previous natural SARS-CoV-2 exposure, 18 (95%; 95% CI 75-99) of 19 patients with solid cancer, 12 (100%; 76-100) of 12 healthy controls, and three (60%; 23-88) of five patients with haematological cancers were seropositive, compared with ten (30%; 17-47) of 33, 18 (86%; 65-95) of 21, and four (11%; 4-25) of 36, respectively, who did not receive a boost. The vaccine was well tolerated; no toxicities were reported in 75 (54%) of 140 patients with cancer following the first dose of BNT162b2, and in 22 (71%) of 31 patients with cancer following the second dose. Similarly, no toxicities were reported in 15 (38%) of 40 healthy controls after the first dose and in five (31%) of 16 after the second dose. Injection-site pain within 7 days following the first dose was the most commonly reported local reaction (23 [35%] of 65 patients with cancer; 12 [48%] of 25 healthy controls). No vaccine-related deaths were reported. INTERPRETATION: In patients with cancer, one dose of the BNT162b2 vaccine yields poor efficacy. Immunogenicity increased significantly in patients with solid cancer within 2 weeks of a vaccine boost at day 21 after the first dose. These data support prioritisation of patients with cancer for an early (day 21) second dose of the BNT162b2 vaccine. FUNDING: King's College London, Cancer Research UK, Wellcome Trust, Rosetrees Trust, and Francis Crick Institute.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/immunology , Neoplasms/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , COVID-19/blood , COVID-19/complications , COVID-19/virology , COVID-19 Vaccines/immunology , Dose-Response Relationship, Immunologic , Female , Humans , Immunogenicity, Vaccine/immunology , London/epidemiology , Male , Middle Aged , Neoplasms/blood , Neoplasms/complications , Neoplasms/virology , Prospective Studies , SARS-CoV-2 , Wales
4.
Theranostics ; 11(14): 7005-7017, 2021.
Article in English | MEDLINE | ID: covidwho-1524524

ABSTRACT

The tumor suppressor protein p53 remains in a wild type but inactive form in ~50% of all human cancers. Thus, activating it becomes an attractive approach for targeted cancer therapies. In this regard, our lab has previously discovered a small molecule, Inauhzin (INZ), as a potent p53 activator with no genotoxicity. Method: To improve its efficacy and bioavailability, here we employed nanoparticle encapsulation, making INZ-C, an analog of INZ, to nanoparticle-encapsulated INZ-C (n-INZ-C). Results: This approach significantly improved p53 activation and inhibition of lung and colorectal cancer cell growth by n-INZ-C in vitro and in vivo while it displayed a minimal effect on normal human Wi38 and mouse MEF cells. The improved activity was further corroborated with the enhanced cellular uptake observed in cancer cells and minimal cellular uptake observed in normal cells. In vivo pharmacokinetic evaluation of these nanoparticles showed that the nanoparticle encapsulation prolongates the half-life of INZ-C from 2.5 h to 5 h in mice. Conclusions: These results demonstrate that we have established a nanoparticle system that could enhance the bioavailability and efficacy of INZ-C as a potential anti-cancer therapeutic.


Subject(s)
Antineoplastic Agents/pharmacology , Colorectal Neoplasms/drug therapy , Indoles/pharmacology , Lung Neoplasms/drug therapy , Nanoparticles/chemistry , Phenothiazines/pharmacology , Tumor Suppressor Protein p53/metabolism , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Biological Availability , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Humans , Indoles/chemistry , Indoles/pharmacokinetics , Indoles/therapeutic use , Mice , Mice, Inbred C57BL , Microscopy, Electron, Transmission , Nanoparticles/toxicity , Nanoparticles/ultrastructure , Phenothiazines/chemistry , Phenothiazines/pharmacokinetics , Phenothiazines/therapeutic use , Spectroscopy, Fourier Transform Infrared , Tumor Suppressor Protein p53/genetics , Xenograft Model Antitumor Assays
5.
Oncology (Williston Park) ; 35(1): 26-28, 2021 Jan 11.
Article in English | MEDLINE | ID: covidwho-1485807

ABSTRACT

Against the difficult and trying backdrop of the pandemic, cancer investigators persisted, and for patients with lung cancer, that persistence paid off in spectacular ways. With several new FDA approved treatments, as well as 2 new targetable mutations in non-small cell lung cancer (NSCLC), 2020 was a banner year in the overall lung cancer space. ONCOLOGY® recently sat down with Jennifer W. Carlisle, MD, of Emory University's Winship Cancer Institute, to discuss the many advances made during the last year for patients with lung cancer along with her hopes for further significant milestones in the year to come.


Subject(s)
COVID-19/epidemiology , Lung Neoplasms/drug therapy , Medical Oncology/organization & administration , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Humans , Lung Neoplasms/genetics , Precision Medicine , SARS-CoV-2
6.
J Clin Oncol ; 39(20): 2232-2246, 2021 07 10.
Article in English | MEDLINE | ID: covidwho-1484813

ABSTRACT

PURPOSE: Variation in risk of adverse clinical outcomes in patients with cancer and COVID-19 has been reported from relatively small cohorts. The NCATS' National COVID Cohort Collaborative (N3C) is a centralized data resource representing the largest multicenter cohort of COVID-19 cases and controls nationwide. We aimed to construct and characterize the cancer cohort within N3C and identify risk factors for all-cause mortality from COVID-19. METHODS: We used 4,382,085 patients from 50 US medical centers to construct a cohort of patients with cancer. We restricted analyses to adults ≥ 18 years old with a COVID-19-positive or COVID-19-negative diagnosis between January 1, 2020, and March 25, 2021. We followed N3C selection of an index encounter per patient for analyses. All analyses were performed in the N3C Data Enclave Palantir platform. RESULTS: A total of 398,579 adult patients with cancer were identified from the N3C cohort; 63,413 (15.9%) were COVID-19-positive. Most common represented cancers were skin (13.8%), breast (13.7%), prostate (10.6%), hematologic (10.5%), and GI cancers (10%). COVID-19 positivity was significantly associated with increased risk of all-cause mortality (hazard ratio, 1.20; 95% CI, 1.15 to 1.24). Among COVID-19-positive patients, age ≥ 65 years, male gender, Southern or Western US residence, an adjusted Charlson Comorbidity Index score ≥ 4, hematologic malignancy, multitumor sites, and recent cytotoxic therapy were associated with increased risk of all-cause mortality. Patients who received recent immunotherapies or targeted therapies did not have higher risk of overall mortality. CONCLUSION: Using N3C, we assembled the largest nationally representative cohort of patients with cancer and COVID-19 to date. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Full characterization of the cohort will provide further insights into the effects of COVID-19 on cancer outcomes and the ability to continue specific cancer treatments.


Subject(s)
COVID-19/therapy , Neoplasms/mortality , Adolescent , Adult , Aged , COVID-19/diagnosis , COVID-19/mortality , Case-Control Studies , Cause of Death , Electronic Health Records , Female , Humans , Male , Middle Aged , Neoplasms/diagnosis , Neoplasms/therapy , Prognosis , Registries , Risk Assessment , Risk Factors , Time Factors , United States , Young Adult
7.
Heliyon ; 6(4): e03795, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-1454150

ABSTRACT

A temporary discontinuation (drug holiday) of high-dose antiresorptive (AR) agents has been proposed to reduce the risk of medication-related osteonecrosis of the jaw (MRONJ). The aim of this systematic review was to answer the question: Is high-dose AR drug holiday, at the time of tooth extraction or dentoalveolar surgery, necessary to prevent the development of MRONJ in patients with cancer? This protocol was registered in the PROSPERO database. Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant studies up to and including April 2019. Randomized controlled trials (RCTs), cohort and cross-sectional studies, surveys, and case reports with more than five patients were included. Records were imported into www.covidence.org. Electronic searches were supplemented by manual searches and reference linkage. The Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) were followed. Although only one study fitted the population, intervention, comparison, outcome (PICO) framework, valuable information on AR drug holiday could be extracted from 14 of 371 reviewed articles. Among these, 3 were prospective and 11 were retrospective studies. These studies described or evaluated high-dose AR drug holidays. In 2 studies, patients were being treated with denosumab, but neither showed that a drug holiday was effective. The remaining 12 studies evaluated bisphosphonate treatment and 2 of these studies found no reason to use AR drug holiday before surgery. Three studies recommended drug holidays, whereas most of the studies recommended assessing each patient separately. The only paper that fitted the PICO approach was a non-randomized, prospective study with a control group. This study concluded that drug holiday was not necessary. Thus, there are no evidence for using drug holiday, but it is also clear that caused by a limited numbers of eligible patients, and a great variation in between these patient, high-level evidence for using AR drug holiday is almost impossible to obtain.

8.
Vaccines (Basel) ; 9(3)2021 Mar 11.
Article in English | MEDLINE | ID: covidwho-1448935

ABSTRACT

The mRNA-based vaccine approach is a promising alternative to traditional vaccines due to its ability for prompt development, high potency, and potential for secure administration and low-cost production. Nonetheless, the application has still been limited by the instability as well as the ineffective delivery of mRNA in vivo. Current technological improvements have now mostly overcome these concerns, and manifold mRNA vaccine plans against various forms of malignancies and infectious ailments have reported inspiring outcomes in both humans and animal models. This article summarizes recent mRNA-based vaccine developments, advances of in vivo mRNA deliveries, reflects challenges and safety concerns, and future perspectives, in developing the mRNA vaccine platform for extensive therapeutic use.

10.
J Med Virol ; 93(10): 5839-5845, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1432415

ABSTRACT

Undoubtedly, cancer patients have suffered the most from the COVID-19 pandemic process. However, cancer is a heterogeneous disease, and each patient has responded differently to COVID-19. We aimed to describe the clinical characteristics and outcomes of patients with cancer and COVID-19. We retrospectively reviewed 45 cancer patients hospitalized in the Cerrahpasa Medical Faculty COVID-19 department from March 23 to October 23, 2020. We analyzed the demographic characteristics, symptoms, laboratory findings, treatment, prognosis, and cancer subtypes of patients and mortality who were hospitalized for COVID-19. Between March 23 and October 23, 2020, 45 hospitalized cancer patients who had laboratory-confirmed COVID-19 infection were included, with a median age of 60 years (range: 23-92). Patients were divided into two groups a survivor and a non-survivor. Symptoms, demographic information, comorbidities, treatments for COVID-19, and laboratory findings of the two groups were evaluated separately. Two parameters were found, which showed a significant difference between non-survivors and survivors displaying a disadvantage for COPD and low platelet count (p = 0.044-0.038). The mortality rate of all patients was 66%. The presence of comorbidities such as COPD and low platelet count in cancer patients with COVID-19 infection may draw the attention of physicians.


Subject(s)
COVID-19/epidemiology , Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Humans , Male , Middle Aged , Neoplasms/classification , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2 , Turkey/epidemiology
11.
Memo ; 14(1): 1-2, 2021.
Article in English | MEDLINE | ID: covidwho-1401094
12.
Anticancer Res ; 41(6): 2745-2757, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1404214

ABSTRACT

BACKGROUND/AIM: Seventy-six years after Auschwitz Liberation, the Holocaust keeps on persecuting its surviving victims. As witnessed by the psychiatric and medical literature in the last decades, in fact, the Holocaust survivors (HS) appear to suffer from several Shoah-related late-onset diseases impacting their survival, such as internal illnesses and post-traumatic stress disorder (PTSD). Cancer represents a further severe pathology which seems to be connected with the Holocaust experience. Our aim was to review the existing knowledge of Holocaust-related cancer in HS in order to assess its real incidence and clinicoprognostic significance. MATERIALS AND METHODS: We systematically reviewed the literature dealing with Israeli Jewish and non-Jewish non-Israeli HS developing cancer. We also reviewed and analyzed the cancer data of noted Jewish HS not resident or having resided in Israel available as public information. RESULTS: We found 16 and 15 studies on Israeli Jews and non-Jewish non-Israeli survivors, respectively. A statistically significant association between the Holocaust and development of late-onset cancer in HS was seen in most studies with cancer adversely impacting the survival. We also selected 330 noted Jewish non-Israeli HS: genocide-related late-onset cancer resulted to be a significant and independent risk factor of poor prognosis (p<0.0001) imparting shorter survival in affected versus non-cancer subjects (57 versus 64 years, respectively, p=0.0001). CONCLUSION: Although 76 years have passed, our review shows how the Holocaust keeps on burdening its survivors. Moreover, we offered the first analysis of Jewish HS not resident or having resided in Israel in terms of genocide-related late-onset diseases focusing on cancer. Further studies on Jewish non-Israeli HS are needed in order to corroborate our findings on late-onset cancer occurring in this targeted population.


Subject(s)
Holocaust/psychology , Jews , Neoplasms/etiology , Survivors/psychology , Age of Onset , Aged , Humans , Israel , Neoplasms/epidemiology , Neoplasms/pathology , Risk Factors , Survival Analysis
13.
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
14.
Ecancermedicalscience ; 15: 1189, 2021.
Article in English | MEDLINE | ID: covidwho-1394745

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic presents serious challenges to cancer care because of the associated risks from the infection itself and the disruption of care delivery. Therefore, many professional societies have published recommendations to help manage patients with cancer during the current pandemic. The objective of our study is to assess the national responses of Middle East North Africa (MENA) countries in terms of publishing relevant guidelines and analyse various components of these guidelines. METHODS: A survey based on the preliminary review of the literature regarding cancer care adaptations has been developed and then completed by a group of oncologists from the following Arab countries affected by the pandemic: Algeria, Egypt, Iraq, Jordan, Kuwait, Lebanon, Morocco, Oman, Saudi Arabia, Syria, Tunisia, United Arab Emirates and Yemen. The survey inquired about COVID-19 cases, national recommendations regarding general measures of COVID-19 prevention and patient care in oncology as well as their implementation about cancer care adaptations during the pandemic. RESULTS: Analysis of the COVID-19 pandemic-related guidelines revealed at least 30 specific recommendations that we categorised into seven essential components. All included countries had national guidelines except one country. Estimated full compliances with all specific category recommendations ranged from 30% to 69% and partial compliance ranged from 23% to 61%. CONCLUSION: There is a very good response and preparedness in the Arab Middle East and North Africa region surveyed. However, there are inconsistencies in the various components of the guidelines across the region, which reflects the evolving status of the pandemic in each country as well as the lack of clear evidence-based guidelines for many of the issues in question. There is a need for a clear framework on essential components that should be included in these guidelines to assure providing the best guidance to the oncology community.

15.
Sci Rep ; 11(1): 2459, 2021 01 28.
Article in English | MEDLINE | ID: covidwho-1387462

ABSTRACT

A deeper understanding of the molecular biology of SARS-CoV-2 infection, including the host response to the virus, is urgently needed. Commonalities exist between the host immune response to viral infections and cancer. Here, we defined transcriptional signatures of SARS-CoV-2 infection involving hundreds of genes common across lung adenocarcinoma cell lines (A549, Calu-3) and normal human bronchial epithelial cells (NHBE), with additional signatures being specific to one or both adenocarcinoma lines. Cross-examining eight transcriptomic databases, we found that host transcriptional responses of lung adenocarcinoma cells to SARS-CoV-2 infection shared broad similarities with host responses to multiple viruses across different model systems and patient samples. Furthermore, these SARS-CoV-2 transcriptional signatures were manifested within specific subsets of human cancer, involving ~ 20% of cases across a wide range of histopathological types. These cancer subsets show immune cell infiltration and inflammation and involve pathways linked to the SARS-CoV-2 response, such as immune checkpoint, IL-6, type II interferon signaling, and NF-κB. The cell line data represented immune responses activated specifically within the cancer cells of the tumor. Common genes and pathways implicated as part of the viral host response point to therapeutic strategies that may apply to both SARS-CoV-2 and cancer.


Subject(s)
COVID-19/genetics , Host Microbial Interactions/physiology , SARS-CoV-2/physiology , A549 Cells , Bronchi/metabolism , COVID-19/metabolism , Epithelial Cells/metabolism , Epithelial Cells/virology , Humans , Immunity , Lung Neoplasms/pathology , Lung Neoplasms/virology , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Transcription, Genetic , Transcriptome , Virus Replication/genetics
16.
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
17.
J Cancer Res Clin Oncol ; 147(5): 1469-1479, 2021 May.
Article in English | MEDLINE | ID: covidwho-1384445

ABSTRACT

INTRODUCTION: The severe acute respiratory syndrome-2 (SARS-CoV-2) pandemic disrupted medical care for persons with cancer including those with lymphoma. Many professional societies recommend postponing, decreasing, or stopping anti-cancer therapy in selected persons during the pandemic. Although seemingly sensible, these recommendations are not evidence-based and their impact on anxiety and health-related quality-of-life (HRQoL) is unknown. METHODS: We surveyed 2532 subjects including 1060 persons with lymphoma, 948 caregivers, and 524 normals using a purposed-designed questionnaire on a patient organization website. Respondents also completed the Zung Self-Rating Anxiety and patient respondents, the EORTC QLQ-C30 instruments to quantify anxiety, and HRQoL. We also evaluated caregiver support and an online education programme of the Chinese Society of Clinical Oncology (CSCO). Data of HRQoL from a 2019 pre-pandemic online survey of 1106 persons with lymphoma were a control. RESULTS: 33% (95% confidence interval [CI] 30, 36%) of lymphoma patients and 31% (28, 34%) of caregivers but only 21% (17, 24%) of normals had any level of anxiety (both pair-wise P < 0.001). Among lymphoma respondents, physical exercise and better caregiver support were associated with less anxiety, whereas female sex, receiving therapy, and reduced therapy intensity were associated with more anxiety. Paradoxically, lymphoma respondents during the pandemic had better HRQoL than pre-pandemic controls. Reduced therapy intensity was associated with worse HRQoL, whereas respondents who scored caregiver support and the online patient education programme high had better HRQoL. CONCLUSION: During the SARS-CoV-2 pandemic, lymphoma patients and their caregivers had significantly higher incidences of anxiety compared with normals. Lymphoma respondents reported better HRQoL compared with pre-pandemic controls. Reduced therapy intensity in persons with cancer may have unanticipated adverse effects on anxiety and HRQoL. Regular and intense support by caregivers and online education programmes alleviate anxiety and improve HRQoL.


Subject(s)
Anxiety/epidemiology , COVID-19/psychology , Lymphoma/therapy , Quality of Life/psychology , Withholding Treatment/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Caregivers/psychology , Depression/epidemiology , Female , Humans , Internet , Lymphoma/psychology , Male , Middle Aged , Psychosocial Support Systems , Risk , SARS-CoV-2 , Surveys and Questionnaires , Young Adult
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