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1.
Viruses ; 14(4)2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35458542

RESUMO

Human cytomegalovirus (HCMV) is a herpesvirus that alternates lytic and latent infection, infecting between 40 and 95% of the population worldwide, usually without symptoms. During its lytic cycle, HCMV can result in fever, asthenia, and, in some cases, can lead to severe symptoms such as hepatitis, pneumonitis, meningitis, retinitis, and severe cytomegalovirus disease, especially in immunocompromised individuals. Usually, the host immune response keeps the virus in a latent stage, although HCMV can reactivate in an inflammatory context, which could result in sequential lytic/latent viral cycles during the lifetime and thereby participate in the HCMV genomic diversity in humans and the high level of HCMV intrahost genomic variability. The oncomodulatory role of HCMV has been reported, where the virus will favor the development and spread of cancerous cells. Recently, an oncogenic role of HCMV has been highlighted in which the virus will directly transform primary cells and might therefore be defined as the eighth human oncovirus. In light of these new findings, it is critical to understand the role of the immune landscape, including the tumor microenvironment present in HCMV-harboring tumors. Finally, the oncomodulatory/oncogenic potential of HCMV could lead to the development of novel adapted therapeutic approaches against HCMV, especially since immunotherapy has revolutionized cancer therapeutic strategies and new therapeutic approaches are actively needed, particularly to fight tumors of poor prognosis.


Assuntos
Infecções por Citomegalovirus , Neoplasias , Carcinogênese/genética , Citomegalovirus/fisiologia , Humanos , Imunoterapia , Neoplasias/virologia , Oncogenes , Microambiente Tumoral
2.
Int J Mol Sci ; 23(4)2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35216085

RESUMO

The equine sarcoid is one of the most common neoplasias in the Equidae family. Despite the association of this tumor with the presence of bovine papillomavirus (BPV), the molecular mechanism of this lesion has not been fully understood. The transgenization of equine adult cutaneous fibroblast cells (ACFCs) was accomplished by nucleofection, followed by detection of molecular modifications using high-throughput NGS transcriptome sequencing. The results of the present study confirm that BPV-E4- and BPV-E1^E4-mediated nucleofection strategy significantly affected the transcriptomic alterations, leading to sarcoid-like neoplastic transformation of equine ACFCs. Furthermore, the results of the current investigation might contribute to the creation of in vitro biomedical models suitable for estimating the fates of molecular dedifferentiability and the epigenomic reprogrammability of BPV-E4 and BPV-E4^E1 transgenic equine ACFC-derived sarcoid-like cell nuclei in equine somatic cell-cloned embryos. Additionally, these in vitro models seem to be reliable for thoroughly recognizing molecular mechanisms that underlie not only oncogenic alterations in transcriptomic signatures, but also the etiopathogenesis of epidermal and dermal sarcoid-dependent neoplastic transformations in horses and other equids. For those reasons, the aforementioned transgenic models might be useful for devising clinical treatments in horses afflicted with sarcoid-related neoplasia of cutaneous and subcutaneous tissues.


Assuntos
Fibroblastos/virologia , Doenças dos Cavalos/virologia , Cavalos/virologia , Neoplasias/virologia , Papillomaviridae/genética , Sarcoidose/virologia , Dermatopatias/virologia , Animais , Animais Geneticamente Modificados/virologia , Equidae/virologia , Infecções por Papillomavirus/virologia , Pele/virologia , Transcriptoma/genética
3.
EMBO Rep ; 23(4): e52984, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35107856

RESUMO

Telomerase plays a pivotal role in tumorigenesis by both telomere-dependent and telomere-independent activities, although the underlying mechanisms are not completely understood. Using single-sample gene set enrichment analysis (ssGSEA) across 9,264 tumour samples, we observe that expression of telomerase reverse transcriptase (TERT) is closely associated with immunosuppressive signatures. We demonstrate that TERT can activate a subclass of endogenous retroviruses (ERVs) independent of its telomerase activity to form double-stranded RNAs (dsRNAs), which are sensed by the RIG-1/MDA5-MAVS signalling pathway and trigger interferon signalling in cancer cells. Furthermore, we show that TERT-induced ERV/interferon signalling stimulates the expression of chemokines, including CXCL10, which induces the infiltration of suppressive T-cell populations with increased percentage of CD4+ and FOXP3+ cells. These data reveal an unanticipated role for telomerase as a transcriptional activator of ERVs and provide strong evidence that TERT-mediated ERV/interferon signalling contributes to immune suppression in tumours.


Assuntos
Retrovirus Endógenos , Neoplasias , Telomerase , Microambiente Tumoral , RNA Polimerases Dirigidas por DNA/metabolismo , Retrovirus Endógenos/genética , Humanos , Neoplasias/imunologia , Neoplasias/virologia , Telomerase/genética , Telomerase/metabolismo , Telômero/metabolismo , Microambiente Tumoral/genética
4.
Viruses ; 14(2)2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35215833

RESUMO

In 2014 and 2021, two nucleic-acid vaccine candidates named MAV E2 and VGX-3100 completed phase III clinical trials in Mexico and U.S., respectively, for patients with human papillomavirus (HPV)-related, high-grade squamous intraepithelial lesions (HSIL). These well-tolerated but still unlicensed vaccines encode distinct HPV antigens (E2 versus E6+E7) to elicit cell-mediated immune responses; their clinical efficacy, as measured by HSIL regression or cure, was modest when compared with placebo or surgery (conization), but both proved highly effective in clearing HPV infection, which should help further optimize strategies for enhancing vaccine immunogenicity, toward an ultimate goal of preventing malignancies in millions of patients who are living with persistent, oncogenic HPV infection but are not expected to benefit from current, prophylactic vaccines. The major roadblocks to a highly efficacious and practical product remain challenging and can be classified into five categories: (i) getting the vaccines into the right cells for efficient expression and presentation of HPV antigens (fusion proteins or epitopes); (ii) having adequate coverage of oncogenic HPV types, beyond the current focus on HPV-16 and -18; (iii) directing immune protection to various epithelial niches, especially anogenital mucosa and upper aerodigestive tract where HPV-transformed cells wreak havoc; (iv) establishing the time window and vaccination regimen, including dosage, interval and even combination therapy, for achieving maximum efficacy; and (v) validating therapeutic efficacy in patients with poor prognosis because of advanced, recurrent or non-resectable malignancies. Overall, the room for improvements is still large enough that continuing efforts for research and development will very likely extend into the next decade.


Assuntos
Vacinas Anticâncer/uso terapêutico , Neoplasia Intraepitelial Cervical/terapia , Neoplasias/terapia , Infecções por Papillomavirus/terapia , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/terapia , Vacinas de DNA/uso terapêutico , Animais , Neoplasia Intraepitelial Cervical/imunologia , Ensaios Clínicos como Assunto , Feminino , Humanos , Imunogenicidade da Vacina , Neoplasias/imunologia , Neoplasias/virologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Lesões Intraepiteliais Escamosas Cervicais/terapia , Neoplasias do Colo do Útero/virologia , Vacinas de DNA/imunologia , /uso terapêutico
5.
Viruses ; 14(2)2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-35215856

RESUMO

Infection with certain types of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) viruses, known as tumor viruses or oncogenic viruses, can lead to cancer [...].


Assuntos
Neoplasias/virologia , Vírus Oncogênicos , Infecções Tumorais por Vírus/virologia , Animais , Interações Hospedeiro-Patógeno , Humanos , Neoplasias/terapia , Neoplasias/veterinária , Infecções Tumorais por Vírus/terapia , Infecções Tumorais por Vírus/veterinária
6.
Asian Pac J Cancer Prev ; 23(2): 445-450, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35225455

RESUMO

OBJECTIVE: To determine the predictive factors of neutropenia in human immunodeficiency virus (HIV)-infected patients with malignancy receiving chemotherapy (CMT) or radiotherapy (RT). MATERIALS AND METHODS: The author conducted a retrospective study on HIV-infected patients with malignancy receiving CMT or RT at Vajira Hospital, Navamindradhiraj University, Thailand, from January 1, 2013 to December 31, 2017. Baseline demographic characteristics, HIV disease data, and cancer data were collected. RESULTS: A total of 210 courses of CMT, concurrent chemoradiation therapy (CCRT), or RT treatments were administered to 39 HIV-infected patients with malignancy. Neutropenia occurred in 51 (24.3%) of the 210 treatment courses in 23 (60%) patients. Multivariable analysis revealed that HIV-infected patients with malignancy who received CMT or CCRT (hazard ratio [HR] 10.83, 95% confidence interval [CI] 1.36-86.05, p = 0.024) and those who received over five cycles of CMT (HR 5.25, 95% CI 1.10-26.01, p = 0.037) were independently associated with neutropenia. CONCLUSION: Receiving CMT or CCRT and receiving more than five cycles of CMT are risk factors for neutropenia in HIV-infected patients with malignancy.


Assuntos
Antineoplásicos/efeitos adversos , Infecções por HIV/complicações , Neoplasias/terapia , Neutropenia/etiologia , Radioterapia/efeitos adversos , Quimiorradioterapia/efeitos adversos , Feminino , HIV , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/virologia , Estudos Retrospectivos , Fatores de Risco , Tailândia
7.
J Hematol Oncol ; 15(1): 15, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-35123511

RESUMO

PURPOSE: Patients with cancer have an increased risk of coronavirus disease 2019 (COVID-19) and an attenuated responses to various vaccines. This meta-analysis aims to assess the serologic response to COVID-19 vaccination in patients with cancer. METHODS: Electronic databases were systematically searched on August 1, 2021 for studies that reported the serologic response to COVID-19 vaccine in cancer patients. Random effects models were used to achieve pooled serologic response rates and odds ratios (ORs). RESULTS: We analyzed 16 observational studies with a total of 1453 patients with cancer. A majority of studies used mRNA vaccines (BNT162b2 or mRNA-1273). The proportion of patients achieving a serologic response after a single and two doses of COVID-19 vaccine were 54.2% (95% confidence interval [CI] 41.0-66.9) and 87.7% (95% CI 82.5-91.5), respectively. Patients with hematologic cancers had a lower response rate after the second dose of vaccine compared to those with solid organ cancers (63.7% vs. 94.9%), which was attributable to the low response rates associated with certain conditions (chronic lymphocytic leukemia, lymphoma) and therapies (anti-CD20, kinase inhibitors). A lower proportion of patients with cancer achieved a serologic response compared to control patients after one and two doses of vaccine (OR0.073 [95% CI 0.026-0.20] and 0.10 [95% CI 0.039-0.26], respectively). CONCLUSIONS: Patients with cancer, especially those with hematologic B-cell malignancies, have a lower serologic response to COVID-19 vaccines. The results suggest that cancer patients should continue to follow safety measures including mask-wearing after vaccination and suggest the need for additional strategies for prophylaxis.


Assuntos
Teste Sorológico para COVID-19/métodos , Vacinas contra COVID-19/imunologia , COVID-19/complicações , Neoplasias/imunologia , SARS-CoV-2/patogenicidade , COVID-19/sangue , COVID-19/terapia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Humanos , Neoplasias/sangue , Neoplasias/terapia , Neoplasias/virologia , Prognóstico , SARS-CoV-2/isolamento & purificação , Taxa de Sobrevida
8.
PLoS One ; 17(2): e0262784, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35108300

RESUMO

INTRODUCTION: Even if now we have available the weapon of vaccination against SARS-CoV-2, the patients with cancer remains a very frail population in which frequently the immunologic response to vaccination may be impaired. In this setting, the SARS-CoV-2 infection screening retains a great value. However, there are still limited data on the feasibility and efficacy of combined screening procedures to assess the prevalence of SARS-CoV-2 infection (including asymptomatic cases) in cancer outpatients undergoing antineoplastic therapy. PATIENTS AND RESULTS: From May 1, 2020, to June 15, 2020, during the first wave of SARS-CoV-2 pandemic, 860 consecutive patients, undergoing active anticancer therapy, were evaluated and tested for SARS-CoV-2 with a combined screening procedure, including a self-report questionnaire, a molecular nasopharyngeal swab (NPS) and a rapid serological immunoassay (for anti-SARS-CoV-2 IgG/IgM antibodies). The primary endpoint of the study was to estimate the prevalence of SARS-CoV-2 infection (including asymptomatic cases) in consecutive and unselected cancer outpatients by a combined screening modality. A total of 2955 SARS-CoV-2 NPS and 860 serological tests, in 475 patients with hematologic cancers and in 386 with solid tumors, were performed. A total of 112 (13%) patients self-reported symptoms potentially COVID-19 related. In 1/860 cases (< 1%) SARS-CoV-2 NPS was positive and in 14 cases (1.62%) the specific serological test was positive (overall prevalence of SARS-CoV-2 infection 1.62%). Of the 112 cases who declared symptoms potentially COVID-19-related, only 2.7% (3/112) were found SARS-CoV-2 positive. CONCLUSIONS: This is the largest study reporting the feasibility of a combined screening procedure (including triage, NPS and serologic test) to evaluate the prevalence of SARS-CoV-2 infection in cancer patients receiving active therapy, during the first epidemic wave and under the restrictive lockdown measures, in one of the active areas of the SARS-CoV-2 circulation. Lacking specific recommendations for the detection of asymptomatic SARS-CoV-2 cases, a combined diagnostic screening might be more effective to detect the exact prevalence of SARS-CoV-2 in neoplastic patient population. The prevalence can obviously change according to the territorial context, the entity of the restrictive measures adopted and the phase of the epidemic curve. However, its exact and real-time knowledge could be important to balance risks/benefits of oncologic treatments, avoiding (if the prevalence is low) the reduction of dose intensity or the selection of less intensive (but also less effective) anti-cancer therapies.


Assuntos
COVID-19/diagnóstico , Neoplasias/complicações , Neoplasias/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais , Infecções Assintomáticas/epidemiologia , COVID-19/complicações , Controle de Doenças Transmissíveis , Comorbidade , Programas de Triagem Diagnóstica/tendências , Feminino , Humanos , Imunoglobulina G , Imunoglobulina M , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Prevalência , SARS-CoV-2/patogenicidade , Testes Sorológicos
9.
Cancer Prev Res (Phila) ; 15(1): 1-2, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34992149

RESUMO

The First Lady of the United States, Dr. Jill Biden, visited the Hollings Cancer Center at the Medical University of South Carolina on October 25, 2021. This Commentary remarks on the administration's goal of directing public attention to cancer screening and prevention as part of an overall effort to recover ground lost in the COVID-19 pandemic, particularly in underserved communities.


Assuntos
COVID-19/complicações , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Pessoas Famosas , Neoplasias/diagnóstico , SARS-CoV-2/isolamento & purificação , COVID-19/virologia , Humanos , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Neoplasias/virologia , Estados Unidos
10.
Ann Hematol ; 101(3): 491-511, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34994811

RESUMO

Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hematological malignancies not undergoing allogeneic or autologous hematopoietic stem cell transplantation or other cellular therapy including diagnostic, prophylactic, and therapeutic aspects. Particularly, strategies of risk adapted pharmacological prophylaxis and vaccination are outlined for different patient groups. This guideline updates the guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) from 2015 "Antiviral prophylaxis in patients with solid tumours and haematological malignancies" focusing on herpes simplex virus and varicella zoster virus.


Assuntos
Neoplasias Hematológicas/virologia , Herpes Genital/terapia , Herpes Simples/terapia , Neoplasias/virologia , Infecção pelo Vírus da Varicela-Zoster/terapia , Ativação Viral , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Gerenciamento Clínico , Alemanha , Herpes Genital/diagnóstico , Herpes Genital/prevenção & controle , Herpes Simples/diagnóstico , Herpes Simples/prevenção & controle , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/isolamento & purificação , Herpesvirus Humano 2/fisiologia , Herpesvirus Humano 3/efeitos dos fármacos , Herpesvirus Humano 3/isolamento & purificação , Herpesvirus Humano 3/fisiologia , Humanos , Vacinação , Infecção pelo Vírus da Varicela-Zoster/diagnóstico , Infecção pelo Vírus da Varicela-Zoster/prevenção & controle , Ativação Viral/efeitos dos fármacos
11.
BMC Vet Res ; 18(1): 32, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027055

RESUMO

BACKGROUND: Subgroup J avian leukosis virus (ALV-J) is an oncovirus which can induce multiple types of tumors in chicken. In this report, we found novel ALV-J infection is closely associated with serious hepatomegaly and splenomegaly in chicken. CASE PRESENTATION: The layer chickens from six flocks in Jiangsu province, China, showed serious hemoperitoneum, hepatomegaly and splenomegaly. Histopathological results indicated focal lymphocytic infiltration, cell edema and congestion in the liver, atrophy and depletion of lymphocyte in the spleen. Tumor cells were not detected in all the organs. avian hepatitis E virus (aHEV), which is thought to be the cause of a very similar disease, big liver and spleen disease (BLS), was not detected. Other viruses causing tumors or liver damage including Marek's disease virus (MDV), reticuloendotheliosis virus (REV), fowl adenovirus (FAdV) and chicken infectious anemia virus (CIAV) were also proved negative by either PCR or RT-PCR. However, we did detect ALV-J in those chickens using PCR. Only novel ALV-J strains were efficiently isolated from these chicken livers. CONCLUSIONS: This is the first report that chicken hepatomegaly and splenomegaly disease was closely associated with novel ALV-J, highlighting the importance of ALV-J eradication program in China.


Assuntos
Leucose Aviária , Hepatomegalia , Neoplasias , Doenças das Aves Domésticas , Esplenomegalia , Animais , Leucose Aviária/complicações , Vírus da Leucose Aviária , Galinhas , China , Hepatomegalia/veterinária , Hepatomegalia/virologia , Neoplasias/veterinária , Neoplasias/virologia , Doenças das Aves Domésticas/virologia , Esplenomegalia/veterinária , Esplenomegalia/virologia
12.
PLoS Pathog ; 18(1): e1010200, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35025968

RESUMO

The Epstein-Barr Virus (EBV) is involved in the etiology of multiple hematologic and epithelial human cancers. EBV+ tumors employ multiple immune escape mechanisms, including the recruitment of immunosuppressive regulatory T cells (Treg). Here, we show some EBV+ tumor cells express high levels of the chemokines CCL17 and CCL22 both in vitro and in vivo and that this expression mirrors the expression levels of expression of the EBV LMP1 gene in vitro. Patient samples from lymphoblastic (Hodgkin lymphoma) and epithelial (nasopharyngeal carcinoma; NPC) EBV+ tumors revealed CCL17 and CCL22 expression of both tumor cell-intrinsic and -extrinsic origin, depending on tumor type. NPCs grown as mouse xenografts likewise showed both mechanisms of chemokine production. Single cell RNA-sequencing revealed in vivo tumor cell-intrinsic CCL17 and CCL22 expression combined with expression from infiltrating classical resident and migratory dendritic cells in a CT26 colon cancer mouse tumor engineered to express LMP1. These data suggest that EBV-driven tumors employ dual mechanisms for CCL17 and CCL22 production. Importantly, both in vitro and in vivo Treg migration was effectively blocked by a novel, small molecule antagonist of CCR4, CCR4-351. Antagonism of the CCR4 receptor may thus be an effective means of activating the immune response against a wide spectrum of EBV+ tumors.


Assuntos
Quimiocina CCL17/imunologia , Quimiocina CCL22/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Neoplasias/imunologia , Neoplasias/virologia , Linfócitos T Reguladores/imunologia , Animais , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Xenoenxertos , Doença de Hodgkin/imunologia , Doença de Hodgkin/virologia , Humanos , Camundongos , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/virologia
13.
Int J Biol Sci ; 18(1): 15-29, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34975315

RESUMO

The active immunotherapy concept relies on the use of vaccines that are capable of inducing antitumor immunity, reversion of the suppressive immunological environment, and long-term memory responses. Previously, antitumor vaccines based on a recombinant plasmid (pgDE7h) or a purified protein (gDE7) led to regression of early-established human papillomavirus (HPV)-associated tumors in a preclinical model. In this work, the anticancer vaccines were combined with cisplatin to treat HPV-induced tumors at advanced growth stages. The antitumor effects were evaluated in terms of tumor regression, induction of specific CD8+ T cells, and immune modulation of the tumor microenvironment. Acute toxicity induced by the treatment was measured by weight loss and histological alterations in the liver and kidneys. Our results revealed that the combination of cisplatin with either one of the tested immunotherapies (pgDE7h or gDE7) led to complete tumor regression in mice. Also, the combined treatment resulted in synergistic effects, particularly among mice immunized with gDE7, including activation of systemic and tumor-infiltrating E7-specific CD8+ T cells, tumor infiltration of macrophages and dendritic cells, and prevention of tumor relapses at different anatomical sites. Furthermore, the protocol allowed the reduction of cisplatin dosage and its intrinsic toxic effects, without reducing antitumor outcomes. These results expand our knowledge of active immunotherapy protocols and open perspectives for alternative treatments of HPV-associated tumors.


Assuntos
Vacinas Anticâncer/farmacologia , Cisplatino/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/virologia , Infecções por Papillomavirus/complicações , Animais , Camundongos , Camundongos Endogâmicos C57BL , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Cancer Res Clin Oncol ; 148(1): 31-46, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34705104

RESUMO

BACKGROUND: More than 90% of the adult population globally is chronically infected by the Epstein-Barr virus (EBV). It is well established that EBV is associated with a number of malignancies, and advances in knowledge of EBV-related malignancies are being made every year. Several studies have analysed the global epidemiology and geographic distribution of EBV-related cancers. However, most have only described a single cancer type or subtype in isolation or limited their study to the three or four most common EBV-related cancers. This review will present an overview on the spectrum of cancers linked to EBV based on observations of associations and proportions in the published literature while also using these observations to estimate the incidence and mortality burden of some of these cancers. METHOD: We have reviewed the literature on defining features, distribution and outcomes across six cancers with a relatively large EBV-related case burden: Nasopharyngeal carcinoma (NPC), Gastric carcinoma (GC), Hodgkin lymphoma (HL), Burkitt lymphoma (BL), Diffuse large B-cell lymphoma (DLBCL) and Extranodal NK/T-cell lymphoma, Nasal type (ENKTL-NT). We retrieved published region-specific EBV-related case proportions for NPC, GC, HL and BL and performed meta-analyses on pooled region-specific studies of EBV-related case proportions for DLBCL and ENKTL-NT. We match these pooled proportions with their respective regional incidence and mortality numbers retrieved from a publicly available cancer database. Additionally, we also reviewed the literature on several other less common EBV-related cancers to summarize their key characteristics herein. CONCLUSION: We estimated that EBV-related cases from these six cancers accounted for 239,700-357,900 new cases and 137,900-208,700 deaths in 2020. This review highlights the significant global impact of EBV-related cancers and extends the spectrum of disease that could benefit from an EBV-specific therapeutic.


Assuntos
Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4/patogenicidade , Neoplasias/epidemiologia , Neoplasias/virologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/virologia , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/virologia , Humanos , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/virologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/virologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/virologia , Neoplasias/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/virologia , Vimblastina/uso terapêutico
15.
Nucleic Acids Res ; 50(D1): D1334-D1339, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34718715

RESUMO

Large-scale multi-omics datasets, most prominently from the TCGA consortium, have been made available to the public for systematic characterization of human cancers. However, to date, there is a lack of corresponding online resources to utilize these valuable data to study gene expression dysregulation and viral infection, two major causes for cancer development and progression. To address these unmet needs, we established OncoDB, an online database resource to explore abnormal patterns in gene expression as well as viral infection that are correlated to clinical features in cancer. Specifically, OncoDB integrated RNA-seq, DNA methylation, and related clinical data from over 10 000 cancer patients in the TCGA study as well as from normal tissues in the GTEx study. Another unique aspect of OncoDB is its focus on oncoviruses. By mining TCGA RNA-seq data, we have identified six major oncoviruses across cancer types and further correlated viral infection to changes in host gene expression and clinical outcomes. All the analysis results are integratively presented in OncoDB with a flexible web interface to search for data related to RNA expression, DNA methylation, viral infection, and clinical features of the cancer patients. OncoDB is freely accessible at http://oncodb.org.


Assuntos
Bases de Dados Genéticas , Neoplasias/genética , Software , Viroses/genética , Metilação de DNA/genética , Mineração de Dados , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Internet , Neoplasias/virologia , RNA-Seq , Interface Usuário-Computador , Viroses/virologia
17.
J Cell Biochem ; 123(2): 161-182, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34520596

RESUMO

Viruses are known to cause various diseases in human and also infect other species such as animal plants, fungi, and bacteria. Replication of viruses depends upon their interaction with hosts. Human cells are prone to such unwanted viral infections. Disintegration and reconstitution require host machinery and various macromolecules like DNA, RNA, and proteins are invaded by viral particles. E3 ubiquitin ligases are known for their specific function, that is, recognition of their respective substrates for intracellular degradation. Still, we do not understand how ubiquitin proteasome system-based enzymes E3 ubiquitin ligases do their functional interaction with different viruses. Whether E3 ubiquitin ligases help in the elimination of viral components or viruses utilize their molecular capabilities in their intracellular propagation is not clear. The first time our current article comprehends fundamental concepts and new insights on the different viruses and their interaction with various E3 Ubiquitin Ligases. In this review, we highlight the molecular pathomechanism of viruses linked with E3 Ubiquitin Ligases dependent mechanisms. An enhanced understanding of E3 Ubiquitin Ligase-mediated removal of viral proteins may open new therapeutic strategies against viral infections.


Assuntos
Ubiquitina-Proteína Ligases/fisiologia , Proteínas Virais/fisiologia , Viroses/enzimologia , Replicação Viral/fisiologia , COVID-19/tratamento farmacológico , Transformação Celular Viral/fisiologia , Proteínas Culina/fisiologia , Endossomos/virologia , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Inflamação/enzimologia , Inflamação/virologia , Neoplasias/enzimologia , Neoplasias/virologia , Vírus Oncogênicos/fisiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Proteínas com Motivo Tripartido/fisiologia , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Viroses/imunologia , Viroses/virologia , Replicação Viral/efeitos dos fármacos
18.
Cancer Discov ; 12(1): 7, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34764194

RESUMO

Patients with cancer who had a SARS-CoV-2 infection show enhanced antibody responses following vaccination, including against the highly transmissible Delta variant. The finding that three antigen exposures are beneficial supports the idea of prioritizing booster vaccines for them.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Neoplasias/imunologia , Neoplasias/virologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/imunologia , Humanos , Vacinação/métodos
19.
Future Oncol ; 18(5): 533-541, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34825831

RESUMO

Introduction: The objective of this study was to evaluate the clinical and laboratory outcomes of solid cancer patients who were reinfected with COVID-19. Methods: Patients who were tested negative on the COVID-19 PCR test and those with improved clinical conditions after infection with COVID-19 were enrolled in this study. Patients who received a positive COVID-19 PCR test 28 days after the initial positive PCR test were considered as reinfected. Results: A total of 1024 patients with the diagnosis of solid malignancy and COVID-19 PCR positivity were examined. The reinfection rate was 3.1%. Mortality rate of reinfection was 34.3%. The serum ferritin and creatinine values in reinfection were found to be significantly higher than the first infection (respectively; p = 0.015, p = 0.014). Conclusion: This study has demonstrated one of the first preliminary clinical results of COVID-19 reinfection in solid cancer patients.


Plain language summary Solid cancer patients are at a higher risk than general population in terms of COVID-19 infectivity and COVID-19-associated death and disease. It is also known that COVID-19 infection has a more severe course in immunocompromised patients. Solid cancer patients may be a vulnerable subgroup of patients to reinfection with COVID-19. The rate of reinfection was 3.1% (n = 32) in our study population of 1024 solid cancer patients who were tested positive on a COVID-19 PCR test. The death rate of the patients with solid cancer was 34.3% (n = 11). In addition, we demonstrated that intensive care follow-up is significantly longer during the reinfection period. It was demonstrated that the time between the last dose of chemotherapy for the patients and the reinfection COVID PCR positivity did not affect the death rate. The COVID-19 pandemic has affected people's daily lives and treatments in many aspects. Owing to the high death rate of reinfection, even if cancer patients have reinfection, our approach is to continue cancer treatment as soon as the patient is cured. Finally, we support the priority vaccination of cancer patients.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/complicações , Neoplasias/patologia , Reinfecção/patologia , SARS-CoV-2/patogenicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/patologia , COVID-19/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Neoplasias/virologia , Prognóstico , Reinfecção/virologia , SARS-CoV-2/isolamento & purificação , Taxa de Sobrevida
20.
J Allergy Clin Immunol ; 149(2): 550-556.e2, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34800432

RESUMO

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is characterized by impaired type I interferon activity and a state of hyperinflammation leading to acute respiratory distress syndrome. The complement system has recently emerged as a key player in triggering and maintaining the inflammatory state, but the role of this molecular cascade in severe COVID-19 is still poorly characterized. OBJECTIVE: We aimed at assessing the contribution of complement pathways at both the protein and transcriptomic levels. METHODS: To this end, we systematically assessed the RNA levels of 28 complement genes in the circulating whole blood of patients with COVID-19 and healthy controls, including genes of the alternative pathway, for which data remain scarce. RESULTS: We found differential expression of genes involved in the complement system, yet with various expression patterns: whereas patients displaying moderate disease had elevated expression of classical pathway genes, severe disease was associated with increased lectin and alternative pathway activation, which correlated with inflammation and coagulopathy markers. Additionally, properdin, a pivotal positive regulator of the alternative pathway, showed high RNA expression but was found at low protein concentrations in patients with a severe and critical disease, suggesting its deposition at the sites of complement activation. Notably, low properdin levels were significantly associated with the use of mechanical ventilation (area under the curve = 0.82; P = .002). CONCLUSION: This study sheds light on the role of the alternative pathway in severe COVID-19 and provides additional rationale for the testing of drugs inhibiting the alternative pathway of the complement system.


Assuntos
COVID-19/imunologia , Ativação do Complemento/genética , Via Alternativa do Complemento/genética , Proteínas do Sistema Complemento/genética , Coagulação Intravascular Disseminada/imunologia , SARS-CoV-2/patogenicidade , COVID-19/genética , COVID-19/terapia , COVID-19/virologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares/virologia , Estudos de Casos e Controles , Comorbidade , Proteínas do Sistema Complemento/imunologia , Diabetes Mellitus/genética , Diabetes Mellitus/imunologia , Diabetes Mellitus/terapia , Diabetes Mellitus/virologia , Coagulação Intravascular Disseminada/genética , Coagulação Intravascular Disseminada/terapia , Coagulação Intravascular Disseminada/virologia , Feminino , Regulação da Expressão Gênica , Humanos , Hipertensão/genética , Hipertensão/imunologia , Hipertensão/terapia , Hipertensão/virologia , Lectinas/genética , Lectinas/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/virologia , Properdina/genética , Properdina/imunologia , Respiração Artificial , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Índice de Gravidade de Doença
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